CONTRIBUTIONS  lO 
MEDICAL  AND  BIO 
LOGICAL  RESEARCH 


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1 

CONTRIBUTIONS  TO  \ 

MEDICAL  &  BIOLOGICAL 

RESEARCH  i 


VOLUME  TWO 


THE  LIBRARY 

OF 

THE  UNIVERSITY 

OF  CALIFORNIA 

IRVINE 


EX  LIBRIS 
C.  D.  O'MALLEY,  M.D. 


too 


;covi 


hiidA 


CONTRIBUTIONS 

TO  MEDICAL  AND  BIOLOGICAL 
RESEARCH 

DEDICATED  TO 

5iR  William  Osler 

Bart.,  m.  d.,  f.  r.  s. 

IN  HONOUR  OF  HIS 

SEVENTIETH  BIRTHDAY 

July  la,  1919 

BY 

HIS  PUPILS  AND  CO-WORKERS 

VOLUME  TWO 


NEW  YORK 

PAUL  B.  HOEBER 

M  CM  XIX 


rr^ 


^a 


\\\ 
Ol 

V,  X 


Copyright,  1919, 
By  PAUL  B.  HOEBER 


Printed  in  the  United  States  of  America 


CONTENTS 


VOLUME     TWO 


Rehabilitation  of  the  Disabled  .     . 

The  Choice  and  Training  of  Medi- 
cal Officers  for  the  Air  Forces. 

Personality  and  Disease      .... 

Medical  Examination  of  Men  for 
Military  Service:  Some  of  Its 
Problems,  Lessons,  and  Results    . 

American  Red  Cross  Child  Welfare 
Work  in  France 

Military  Morale 

Phases  of  War  Surgery.  Extensive, 
Highly  Disfiguring  Wounds  of 
the  Face  

A  Psychotic  Episode  in  Roman 
History 


Frank  Billings    .     . 

Thomas  R.  Boggs    . 
Frederic  J.  Farnell . 


Sir  James  Galloway 

J.  H.  Mason  Knox,  Jr 
Edward  L.  Munson 


The  Schematic  Drawing  of  the  Eye 
in  Its  Historic  Development    .    . 

Physicians'  Letters 

Homage  to  Sir  William  Osler.     .     . 

Epidemics    of    Influenza    in     1647, 
1789-90  AND  1807 

VoTUM  Medici 

Sir   William  Osler   and  the  Johns 
Hopkins  Hospital 

An  Appreciation   of   Hermann 
Weber 


Edward  Jenner,  a  Student  of  Medi- 
cine, as  Illustrated  in  His  Letters 

The  Influence  of  Osler  on  Ameri- 
can Medicine 


Servetus  Notes 


Charles  A.  Powers 

Charles  L.  Dana 

Mortimer  Frank 
Fielding  H.  Garrison 
Arpad  G.  Gerster 

Guy  Hinsdale 
Bayard  Holmes  . 

Henry  M.  Hurd 

A.  Jacobi  ,     .     . 

Henry  Barton  Jacobs 

George  M.  Kober 
Leonard  L.  Mackall 


PAGE 

651 

655 
659 

665 

680 
688 

694 

697 

708 
712 
720 

721 
731 

732 

736 

740 

756 
767 


vm 


CONTENTS 


A  Simple  Keyword  System  for  In- 
dexing AND  Classifying  Clinical 
Case  Histories  and  Current  Med- 
ical Literature 

Prothymia:  Note  on  the  Morale- 
Concept  in  Xenophon's  "Cyro- 
pedia" 

The  Medical  History  of  Two 
Crusades  

A  Souvenir  of  the  Macartney 
Museum 

Influence  of  English  Medicine 
upon  American  Medicine  in  Its 
Formative  Period 

he  Eyes  of  the  Burrowing  Owl   . 

The  Regulation  of  the  Red  Blood- 
Cell  Supply 


William  H.  Mercur 

E.  E.  Southard  . 
James  J.  Walsb 
J.  Collins  Warren 

William  H.  Welch 
Casey  A.  Wood  . 

C.  H.  Bunting    . 


The   Action   of   Adrenalin   on   the 
Leucocytes  and  Erythrocytes  .    . 

Studies  on  Blood  Sugar 


David  Murray  Cowie 
Louis  Hamman  . 


Influence  of  Fat  on  Calcium  Metab- 
olism      


On  Contra-lateral  Representation 
in  the  Cerebral  Cortex  of  the 
Peripheral  Blood  Vessels    .    .    . 


B.  Raymond  Hoobler 


Colloid  Chemistry  and  Medicine     . 

A  Few  Thoughts  on  the  Vis  Medica- 
TRix  Nature     ........ 


Sources  of  Intellectual  Power  .    . 

The  Psychology  of  Anticipation  and 
of  Dreams 

Clinical  and  Developmental  Study 
OF  A  Case  of  Ruptured  Aneurysm 
of  the  Right  Anterior  Aortic 
Sinus  of  Valsalva 

Detection  of  Abnormal  Tissues 
within  the  Lungs 


The   Conditions   Presented   in  the 
Heart  and  Kidneys  of  Old  People. 


5.  P.  Kramer     .    . 
Jacques  Loeb       .     . 

Robert  Dawson  Rudolph 
William  Browning  .    . 

Frederick  Peterson  .     . 


Maude  E.  Abbott  .  . 
C.  R.  Bardeen  .  .  . 
W.  T.  Councilman  .     . 


778 

786 
796 
806 

811 

818 

824 

829 
845 

853 

857 
861 

873 
880 

892 

899 
915 
918 


CONTENTS  ix 

PAGX 

Epidemiology  of  Poliomyelitis     .      .     Simon  Flexner       .     .     .     gig 

Hemangioendothelioma  of  the  Liver 
IN  THE  Infant,  and  So-called 
Angiosarcoma John  Foote       ....     935 

The  Production  of  an  ANTiHEMOL-f  ^;„;      ^  p   ^  . 

Symptomless  Obliteration  of  the 
Superior  Vena  Cava Thomas  B.  Futcber     .     .     946 

The  Study  of  Morbid  Anatomy   .  Alexander  G.  Gibson   .     .951 

Leucocytes  and  Protozoa  .     .     .     ■  {H.L.M^PixellGoodricb}     9i8 

Further  Observations  on  the 
Effects  of  Roentgenization  and 
Splenectomy  on  Antibody  Produc- 
tion     Ludvig  Hektoen 

The  Importance  of  Recording  the 
Weight  at  Death Elliott  P.  Joslin     . 


The  Tumor  in  Syphilis  of  the  Liver.  Thomas  McCrae    . 

Splenic  Anemia W.  J.  Mayo     . 

Tumor  Formation  with  Peptic 

Ulcer Charles  G.  Stockton 


973 

983 
985 
991 

1002 


Aneurysm  of  the  Middle  Cerebral 
Artery  in  a  Child  Nine  and  One- 
Half  Years  Old Fritz  B.  Talbot      .     .     .   1004 

Observations  on  Congenital  Hyper- 
trophy OF  the  Pylorus   .... 

The  Cardiovascular  Defective   . 

A  Case  of  Ayerza's  Disease    . 

Description  of  a   Minute  Sarcoma, 
Necessitating     Removal    of    the 
Eyeball,  with  Histological 
Findings 

Intoxication  of  Intestinal  Ob- 
struction      G.  H.  Whipple       .     .     .   1065 

Some  Experiences  and  Observations 
IN  the  Treatment  of  Arterioven- 
ous Aneurysms Rudolph  Matas      .     .     .   1074 

Exstrophy  of  the  Bladder      .     .     .     C.  H.  Mayo     .     .     .     .109 


John  Thomson 

.    lOIO 

Louis  M.  Warfield 

.  103 1 

Aldred  Scott  Warthin  . 

.   1042 

John  E.  Weeks 

.  1060 

CONTENTS 


PAGE 

Some  Notes  on  Achylia  Gastrica  Thomas  R.  Brown       .     .   1 1 1 1 

Epidemic  Pneumonia W.  G.  MacCallum       .     .   1115 

A  Psycho-therapeutic  Clinic  in  the 
Jura  Mountains C.F.Martin    .     .     .     .1123 

The  Life  Chart  and  the  Obligation 
OF  Specifying  Positive  Data  in 
Psychopathological  Diagnosis  .     .     Adolf  M^er     .     .     .     .1128 

Pneumonia   and   Empyema   at   Camp 

Dodge,  Iowa Jos.  L.  Miller  ....   1134 

Clinical  Observations  on  the  Late 

Pulmonary  Effects  of  Gassing  Roger  S.  Morris     .     .     .   1 138 

The  Diagnosis  of  Traumatic 

Hemothorax Geo.W.Norris      .     .     .1143 

The  Peritoneal  Syndrome  in 

Malaria H.  C.  Parsons       .     .     .   1149 

Studies  on  the  Potency  of  Digitalis 

Leaves  from  Various  Sources  .  Joseph  H.  Pratt     .     .     .1155 

Epidemic  Influenza  IN  Children  John  Ruhr  ah    ....   1168 

An  Unusual  Complication  OF  Mumps     Joseph  Sailer   .     .     .     ,1172 

Segmental  Cerebral  Monoplegia     .     William  G.  Spiller      .     .   1175 

The  Relation  of  Thyroid  Secretion 
to  the  Condition  of  the  Skin — and 
Incidentally  to  Old  Age     .     .     .     M.  Allen  Starr       .     .     .1184 

Relation  of  Acute  Infection  to 
Diabetes Alfred  Stengel  .     .     .     .1186 

The  Significance  of   Rickettsia   in 

Relation  to  Disease       ....     Richard  P.  Strong       .     .   1205 

The  Relative  Infrequency  of  Can- 
cer of  the  Uterus  in  Women  of 
THE  Hebrew  Race Hiram  N.  Vineberg     .     .   12 17 

The  Contribution  of  Modern  Psy- 
chiatry TO  General  Medicine  .  William  A.  White       .     .    1226 

The  Tolerance  of  Freshly  Deliv- 
ered Women  to  Excessive  Loss  of 
Blood J.  Whitbridge  Williams    .   1238 

Intratracheal    Pulmonary     Irriga- j  M.  C.  Winternitz)  ,,„, 

TiON \G.H.  Smith  j      '     •   "^^ 

Envoi:  Sir  William  Osler  and  the 
American  Medical  Officer       .     .     Francis  A.  Winter      .     .   1267 


ILLUSTRATIONS 

Illustrating  Phases  of  War  Surgery  (Seven  Plates)  Facing  Page    694 

Hermann  Weber "         "       736 

Reproduction  of  Copperplate  Engraving  of  Ser- 
VETus.     By  C.  Van  Sichem  (1607) "         "       768 

The  Fundus  Oculi  of  the  Burrowing  Owl  (Colored)    "         "       820 

Photograph  of  Gelatin  Treated  with  Silver  Ni- 
trate  "         "       868 

Aneurysm    of    Right   Aortic    Sinus    of   Valsalva, 

Rupturing   into   Right  Ventricle  at  Level  of     "        "     4  ^ 
Pulmonary  Valves  (Two  Plates) ^  ^ 

Model  of  Heart  of  Human  Embryo  (Two  Plates)    .     "         "19 

1903 

Heart  of  Alligator  Mississippiensis "         "       903 

Illustrating  Hemangioendothelioma  of  the  Liver 
IN  the  Infant  (Seven  Plates) "  "       936 

Illustrating  Symptomless  Obliteration  of  the  Su- 
perior Vena  Cava "         "       946 

Leucocytes  and  Protozoa "         **       964 

Illustrating  Tumor  Formation  with  Peptic  Ulcer 

(Three  Plates) "  "      1002 

Illustrating  Congenital  Hypertrophy  of  the  Py- 
lorus (Two  Plates) "  "      1012 

Illustrating    Case    of    Ayerza's    Disease   (Seven 
Plates) "         "      1050 

Illustration  of  Case  of  Minute  Sarcoma     ..."         "     1064 

Illustrating  Treatment  of  Arteriovenous  Aneu- 
rysms (Seventeen  Plates) "  "      1082 

Illustrating    Exstrophy    of    the    Bladder   (Five     «         „  f  1102 
Plates) .- \  1 104 

Rickettsia  Bodies  in  the  Excrement  of  Normal 
Lice "         "     1210 

zi 


CONTRIBUTIONS  TO 

MEDICAL  &  BIOLOGICAL 

RESEARCH 


REHABILITATION  OF  THE  DISABLED 
By  Frank  Billings,  M.D.,  Washington,  D.  C. 

HE  World  War  has  aroused  an  universal 
interest  in  the  physical  and  mental  rehabil- 
itation of  disabled  soldiers.  The  instru- 
ments of  destruction  of  modern  warfare 
sacrificed  so  many  lives  and  disabled  such 
a  multitude  of  men  that  it  became  necessary 
to  utilize  all  possible  measures  to  conserve 
man  power.  There  was  urgent  need  to 
hasten  and  to  make  more  certain  the  res- 
toration of  the  soldier  disabled  by  illness  or  wounds  so  that  he 
could  return  to  military  duty. 

Modern  military  medicine  and  surgery  is  a  development  of  the 
World  War.  It  is  efficient.  Phenomenal  technical  surgical  skill 
and  wise  and  rational  medical  management  contemplate  functional  as 
well  as  physical  restoration.  The  armamentarium  of  the  mihtary 
medical  officer  embraces  in  addition  to  the  knife  and  drugs,  hydro-, 
electro-,  and  thermo-therapy;  passive  and  active  exercise  in  the  form 
of  massage;  of  curative  work  both  manual  and  mental  in  wards, 
shops,  gardens,  and  fields;  of  drill,  calisthenics,  and  physical  culture, 
and  of  sports  and  pastimes  in  and  out  of  doors. 

These  measures  hasten  and  make  more  certain  the  recovery  of 
the  disabled  soldier.  Their  application  maintains  the  constant  interest 
of  the  medical  officers,  nurses,  and  enlisted  personnel  in  the  wel- 
fare of  the  patient.  It  diverts  the  mind  of  the  disabled  man  from  the 
contemplation  of  his  present  suffering  and  future  fate;  the  morale 
of  the  hospital  corps  and  the  patients  is  kept  at  a  high  standard. 

651 


652  REHABILITATION  OF  THE  DISABLED 

Based  upon  available  statistics,  from  80  to  85  per  cent  of  combat- 
injured  soldiers  of  the  allied  armies  returned  to  combat  duty.  From 
5  to  10  per  cent  of  combat-disabled  soldiers,  unfit  for  full  military 
service,  returned  to  special  or  limited  duty.  Of  the  remainder,  unfit 
for  all  military  service,  continued  treatment  was  carried  to  the  fullest 
degree  of  restoration  possible  when  the  nature  of  the  disability  is 
considered.  These  disabled  men  unfit  for  all  military  service  include 
the  blind,  the  deaf,  the  dismembered,  the  severely  gassed,  the  in- 
sane, and  others.  Among  these  must  be  classed  also  those  disabled 
by  illness,  including  tuberculosis,  meningitis,  chronic  nephritis,  or- 
ganic heart  disease,  epilepsy,  insanity,  and  other  morbid  conditions. 

Practically  all  of  the  countries  engaged  in  the  war  have  en- 
deavored, with  more  or  less  success,  to  extend  the  attempt  at  physical 
and  functional  restoration  of  the  disabled  soldier  no  longer  fit  for 
military  duty,  beyond  the  period  of  the  needed  hospital  care.  This 
involves  a  program  of  education  and  training  to  overcome  the 
permanent  physical  handicap  and  to  fit  them  to  become  self- 
sustaining  economic  factors  in  civil  life. 

The  bfind  are  no  longer  left  to  brood  and  lament  to  the  degree 
of  mental  degeneracy.  The  remarkably  efficient  school  for  the  blind 
at  St.  Dunstan's,  organized  and  directed  by  Sir  Arthur  Pearson,  has 
set  an  example  which  will  hereafter  force  all  civilized  governments 
properly  to  educate  and  train  the  adult  population  blinded  in  industrial 
occupations  or  by  disease.  Under  the  Medical  Department  of  the  U. 
S.  Army,  a  school  for  the  blinded  soldiers  and  sailors  modeled  upon  St. 
Dunstan's  is  maintained  at  U.  S.  General  Hospital  No.  7,  Baltimore. 

In  like  manner  deaf  soldiers  are  taught  lip  reading,  and  speech 
defects  are  corrected  by  proper  training.  Coincidentally,  the  dis- 
abled soldier  is  educated  and  trained  better  to  qualify  him  for  his 
old  occupation  or  for  a  new  and  gainful  trade  or  profession. 

The  soldier  who  suff'ers  from  an  improvable  type  of  tuberculosis 
is  given  a  form  of  curative  work,  either  manual  or  mental,  which  will 
divert  him  and  aid  in  the  avoidance  of  hospitalization.  The  conva- 
lescent tuberculosis  patient  is  especially  benefited  by  work  in  the  open 
air,  on  a  protected  porch,  or  in  garden  or  field.  Intelligent  medical 
supervision  as  to  the  dosage  of  work  and  a  common-sense  choice  of 
practical  forms  of  curative  work  are  essential  in  the  treatment  of 
the  tuberculosis  patient. 


REHABILITATION  OF  THE  DISABLED  653 

The  object  of  the  training  and  education  of  dismembered  patients 
is  two-fold.  First,  the  training  of  the  brain  and  of  the  muscles  of 
the  remaining  limb  or  limbs  is  for  the  purpose  of  making  the  one  limb 
perform  the  function  of  two.  The  left  upper  extremity  may  be  trained 
to  do  all  and  more  than  the  lost  right  arm  did.  Properly  fitted 
artificial  legs  may  become,  with  supervised  and  regulated  rational 
practice,  almost  as  useful  as  the  natural  ones.  Second,  training  or 
education  for  fife  employment,  which  may  be  carried  on  coinciden- 
tally  with  the  efforts  to  restore  control  of  a  member  or  to  attain 
what  may  be  termed  vicarious  function. 

One  may  not  contemplate  the  physical  and  mental  rehabilitation 
of  disabled  soldiers  without  a  consideration  of  the  past  and  present 
neglect  of  the  disabled  men  in  the  great  industrial  armies  of  the 
world.  It  has  been  stated  that  750,000  people  are  injured  annually  in 
the  industrial  occupations  of  eighteen  of  the  United  States  of 
America.  That  35,000  of  these  individuals  are  permanently  disabled. 
It  is  also  stated  that  of  people  engaged  in  industrial  occupations, 
80,000  are  permanently  disabled  annually  in  the  whole  United 
States.  Of  these,  2000  are  totally  disabled.  This  enormous  crippHng 
or  entire  loss  annually  of  the  industrial  workers  must  be  met  by  a 
poHcy  of  conservation  and  a  rational  program  of  rehabihtation  of  the 
disabled.  The  experience  of  the  allied  countries  associated  in 
the  World  War  in  the  rehabilitation  of  disabled  soldiers  should  be 
appHed  to  the  disabled  of  the  industrial  army. 

The  policy  of  rehabihtation  of  the  disabled  should  be  the  same 
as  that  appHed  in  military  organizations,  but  the  program  should  be 
modified  to  meet  civiHan  demands  and  conditions.  During  the 
conflict  disabled  soldiers  were  kept  in  the  hospital  or  in  convalescent 
training  centers  until  fit  for  mihtary  service.  The  mihtary  authority 
trained  and  educated  the  disabled  soldier,  no  longer  fit  for  combat 
service,  for  special  or  Hmited  military  duty.  Then  it  was  necessary 
to  organize  educational  and  trade-training  facihties  at  the  mihtary  hos- 
pital, which  was,  necessarily,  more  or  less  an  educational  institution. 

In  civil  fife,  the  chief  function  of  the  hospital  is  to  afford  the 
patients  the  most  efficient  methods  of  medical  and  surgical  care 
and  the  most  certain  and  rapid  physical  and  functional  restoration 
with  due  consideration  of  the  nature  of  the  disabihty.  To  facihtate 
the  physical  and  Junctional  restoration  of  the  patients,  the  hospital 


6s4  REHABILITATION  OF  THE  DISABLED 

must  furnish  efficient,  medical,  surgical,  and  nursing  care,  adequate 
facilities  for  pliysiotherapy,  for  occupational  therapy,  and  for  play 
and  other  amusements.  Occupational  therapy  must  be  applied 
primarily  for  the  purpose  of  functional  cure,  but  the  rational  choice 
of  forms  of  curative  work,  at  the  bedside,  in  shop,  or  elsewhere,  may 
be  essentially  pre-vocational,  or  even  the  primary  steps  of  vocational 
training.  The  more  nearly  curative  work  approaches  occupational 
training,  the  greater  the  therapeutic  value,  because  of  the  gain  in 
useful  knowledge  and  the  consequent  interest  the  patient  takes  in 
the  work  as  a  rule. 

Many  disabled  industrial  workers  will  need  training  and  educa- 
tion to  overcome  the  handicap  of  a  permanent  disability.  This 
training  and  education  is  not  a  function  of  the  hospital.  The  hospital 
has  discharged  its  responsibility  when  the  treatment  of  the  patient 
has  reached  the  stage  of  the  completed  physical  and  functional 
restoration  consistent  with  the  nature  of  the  disability.  But  the 
disabled  industrial  worker  should  have  the  opportunity  for  this 
training  and  education.  If  he  takes  advantage  of  the  opportunity, 
the  training  and  education  will  neutralize  the  handicap  due  to  the  dis- 
ability. He  may  then  return  to  his  old  or  to  a  new  job  an  efficient 
economic  factor  in  the  industrial  world,  instead  of  an  unhappy 
dependent  of  the  government  or  state. 

The  policy  of  rehabihtation  of  the  disabled  and,  by  the  practice 
of  it,  the  conservation  of  man  power  and  of  individual  and  commu- 
nity self-respect  and  happiness,  is  imperatively  demanded.  Provision 
for  its  universal  efficient  application  must  be  made  by  the  govern- 
ment, either  Federal,  State  or  Municipal,  or  by  all  co-operatively. 

Pensions  and  disability  compensation  are  just  measures  for  the  re- 
lief of  permanently  disabled  soldiers  and  injured  industrial  workmen. 
These  measures  of  financial  relief  should  be  continued  as  additional 
aids  in  the  attempt  to  provide  efficient  rehabilitation  of  permanently 
disabled  victims  of  war  and  of  accidents  due  to  industrial  activities. 

The  efficient  application  of  the  complete  rehabilitation  of  per- 
manently disabled  soldiers  and  men  and  women  of  the  industrial 
army  will  materially  lessen  the  inmates  of  soldiers*  homes  and  of 
almshouses.  Only  those  soldiers  and  civilians  whose  disabilities 
are  total  will  seek  refuge  therein. 


THE  CHOICE  AND  TRAINING  OF  MEDICAL 
OFFICERS  FOR  THE  AIR  FORCES 

By  Thomas  R.  Boggs,  M.D.,  Baltimore,  Md., 

Colonel  Med.  Corps,  U.  S.  A.,  (Temp.)  Medical  Consultant,  Air  Service,  A.  E.  F. 

FROM  the  most  ancient  times  medical  men  have  been  interested 
in  the  theoretical  and  speculative  aspects  of  flying,  and  now 
that  the  development  of  modern  warfare  has  brought  hundreds 
of  doctors  into  contact  with  what  is  for  them  an  unexplored  field  of 
professional  activity,  and  practically  forced  the  evolution  of  a  new 
specialty,  it  may  seem  not  altogether  inappropriate  to  discuss 
briefly  some  points  bearing  on  the  selection  and  education  of  medical 
men  for  this  duty,  in  a  volume  prepared  in  honor  of  one  who,  with 
all  his  versatility,  is  perhaps  most  eminent  as  a  teacher  and  molder 
of  ideals  in  the  medical  profession. 

Change  and  adaptation  to  new  conditions  has  been  the  lot  of  the 
doctor  since  medicine  emerged  from  its  enslavement  to  the  doctrines 
of  Galen,  and  the  profession  has  had  many  more  diflicult  adjustments 
to  make  than  those  involved  in  taking  up  the  problems  of  the  flying 
men;  in  fact,  until  the  Great  War  gave  such  impetus  to  the  develop- 
ment of  aeronautics,  very  few  of  the  profession  at  large  had  realized 
that  there  were  any  such  problems.  It  is  not  remarkable,  then, 
that  at  the  beginning  the  assignment  of  medical  officers  to  air  ser- 
vice units  was  more  or  less  fortuitous,  nor  that  the  characters  most 
desirable  in  the  squadron  medical  officer  were  arrived  at  empirically. 
Only  the  test  of  time  brought  out  the  pecuHar  importance  and 
responsibility  of  the  squadron  doctor,  and  made  apparent  the 
differences  between  the  successful  and  the  mediocre,  so  that  a  type 
was  defined  by  a  process  of  gradual  elimination. 

At  the  first  glance  these  men  may  seem  to  have  little  in  common 
in  their  previous  training  and  professional  activities.  One  was  in  civil 
life  an  ophthalmologist,  another  an  obstetrician,  a  third  a  country 
practitioner,  the  next  a  neurologist  or  a  laboratory  worker.  In  age 
they  vary  from  twenty-five  to  nearly  fifty,  though  it  is  less  common 

655 


6s6  TRAINING    FOR  AIR  FORCES 

for  the  very  young  men  to  make  good  in  this  field.  Let  us,  then, 
consider  the  factors,  environmental  and  personal,  which  have 
brought  about  this  development. 

The  basal  unit  of  the  Air  Service  is  the  Squadron,  which  is 
relatively  small,  but  must  be  self-contained,  as  the  exigencies  of  the 
service  may  require  it  to  be  very  much  isolated.  The  proportion  of 
officers  in  this  group  is  very  large,  much  larger  than  in  any  other 
branch  of  the  service.  Again,  the  average  age  of  the  officers  is  very 
low;  they  are  hardly  more  than  boys,  and  still  have  many  of  the 
boy's  characteristics.  These  young  officers  are  engaged  in  a  service 
fraught  with  many  dangers  other  than  those  incurred  in  fighting, 
and  with  factors  of  isolation,  personal  responsibiHty,  and  strain, 
which  are  specially  difficult  for  the  very  young.  Furthermore  these 
fliers  are  relatively  highly  paid,  and  they  have  been  encouraged 
to  consider  themselves  as  a  corps  d' elite,  set  apart  and  different  from 
the  rest  of  the  world.  There  yet  remains  from  the  earfier  and  more 
perilous  days  of  aviation  the  idea  that  these  are  enjants  perdiis,  who 
should  be  excused  for  fiving  vividly  while  Hfe  is  theirs.  Women 
particularly  seek  them  out  and  shower  their  favors  upon  them. 
Lastly,  they  have  been  given  little  discipfinary  training,  in  deference 
to  the  highly  technical  character  of  the  duty  they  perform.  It  is 
hardly  strange,  then,  that,  while  these  young  men  are  essentially 
normal,  they  have  none  the  less  presented  special  problems  for  the 
medical  man.  We  can  make  no  adequate  approach  to  the  medical 
aspects  of  aviation  without  keeping  in  mind  these  factors  and  their 
physical  and  psychological  bearing. 

With  these  facts  in  mind  it  is  easy  to  understand  that  the  doctor 
with  youth  in  his  heart,  tact,  sympathy,  insight,  abiHty  to  five  with 
and  as  the  others  without  sacrificing  their  respect,  frankness, 
courage,  and  a  background  of  sf)ort,  has  stood  pre-eminent.  Such 
traits  have  made  of  the  medical  officer  the  famifiar  friend  and  coun- 
selor, and  it  is  to  such  men  that  these  boys  have  come  with  their 
worries,  physical,  social,  moral,  or  spiritual,  and  have  not  gone  away 
uncomforted. 

To  reach  the  necessary  degree  of  understanding  and  acquire 
the  flier's  respect,  the  aviation  medical  man  must  fly,  at  least  as  a 
passenger.  Only  in  this  way  can  he  understand  the  air  man's  language 
and  think  his  thoughts  or  enter  into  his  experiences.  In  no  other  way 


TRAINING  FOR  AIR  FORCES  657 

can  the  doctor  learn  what  it  means  to  loop,  spin,  dive,  or  make  a 
landing.  Without  these  experiences  in  common  the  doctor  is  kept  at 
arm's  length.  In  brief,  the  squadron  medical  officer's  success  is 
proportional  to  his  humanness  and  practical  psychology. 

In  order  to  measure  up  fully  to  his  responsibiHties,  however,  the 
doctor  in  the  Air  Service  must  have  special  training  in  applied 
physiology,  somatic  and  psychic,  for  the  laboratory  has  made  great 
strides  in  the  study  of  flying  fitness,  the  causes  and  nature  of  flying 
stress  and  fatigue,  the  recognition  of  their  early  symptoms,  and  the 
measures  for  their  prevention  and  treatment.  The  medical  officer 
should  be  able  to  apply  the  simpler  tests  in  the  field,  and  to  decide 
whether  it  is  necessary  to  send  the  flier  to  a  laboratory  for  more 
complete  examination. 

The  aviation  medical  laboratory  is  an  institute  of  applied 
physiology,  which  has  already  proved  itself  indispensable  to  the 
development  of  maximal  efficiency  in  aeronautics.  It  has  a  threefold 
function — the  routine  apphcation  of  special  methods  of  examination 
to  the  individual  flier  in  order  to  determine  his  fitness  or  the  nature 
of  any  disability,  the  instruction  of  medical  officers  for  field  and 
laboratory  service  with  the  air  forces,  and  the  prosecution  of 
researches  into  every  phase  of  physiology,  psychology,  and  medicine 
which  may  affect  man's  adaptation  to  fife  in  the  air. 

In  the  medical  organization  of  the  air  forces,  then,  we  must 
provide  for  two  groups  of  officers  with  rather  different  duties,  the 
field  officers  or  "Fhght  Surgeons"  and  the  laboratory  workers. 
The  fines  may  not  be  too  sharply  drawn,  however,  as  there  should 
be  every  opportunity  for  the  interchange  of  duties.  Indeed,  the 
laboratory  examinations  and  the  research  into  aviation  problems 
can  be  carried  on  much  better  by  men  who  have  had  some  field 
experience  as  well,  or  at  least  have  made  flights  as  passengers. 

It  follows  from  the  foregoing  that  the  aviation  medical  service 
must  be  separated,  at  least  so  far  as  the  personnel  is  concerned, 
from  the  other  branches.  For  it  is  not  economy  to  give  the  medical 
officer  months  of  special  technical  training  only  to  have  him  trans- 
ferred to  some  service  to  which  this  training  is  inappHcable. 

With  regard  to  the  future  in  peace  times,  it  seems  probable  that 
there  will  be  Httle  difficulty  in  supplying  the  laboratories  with 
staffs  sufficient  to  carry  on  the  work,  because  of  the  opportunities 


658  TRAINING  FOR  AIR  FORCES 

for  research.  But  the  field  surgeons  present  a  rather  different  prob- 
lem, as  it  is  unlikely  that  the  narrow  prospects  of  an  army  medical 
career  will  attract  the  highly  gifted  man  we  desire.  Perhaps  this 
contingency  could  be  met  by  limited  periods  of  active  service  in  a 
special  reserve  corps,  and  the  offering  of  training  in  aviation  medicine 
in  our  best-equipped  medical  schools.  In  countries  where  a  form  of 
national  service  prevails  it  should  be  relatively  simple  to  have  a 
reserve  of  trained  doctors  of  the  best  type. 

The  development  of  civil  and  commercial  aviation  may  create  in 
time  ample  scope  for  an  interesting  professional  branch.  But  what- 
ever the  difficulties  to  be  surmounted  as  time  goes  on  we  must 
recognize  now  a  sturdy  neophyte  in  the  Temple  of  Hippocrates,  the 
"Flight  Surgeon,"  at  once  a  foster-son  of  Dsedalus,  a  disciple  of 
Leonardo,  and  a  votary  of  St.  Elias. 


PERSONALITY  AND  DISEASE 
By  Frederic  J.  Farnell,  M.D.,  Providence,  R.  I. 

Psychiatrist  to  Providence  Public  Schools;  Director  of  School  Psychiatric  Clinic;  Neuro- 

Psychiatrist,  Providence  City  Hospital;  Sero- Pathologist,  State  Hospital  for 

Mental  Diseases;  Consulting  Psychiatrist,  St.  Joseph's  Hospital 

and  Sophia  Little  Home  for  Delinquent  Girls,  etc. 

"f^  YNOPTIC  man  is  one  who  sees  the  verities  of  life  in  their 

^^true  relations,  properly  co-ordinated  and  subordinated,  and 

^„y  who,  in  particular  pursuits,  however  absorbing,  does  not  ignore 

the  unity  of  the  whole,  nor  overlook  the  universal  aspect  of  even 

the  commonplaces  of  life." 

I  wish  to  express  my  great  appreciation  to  the  committee  for 
the  compliment  they  have  given  me  in  asking  me  to  contribute 
to  the  Osier  Anniversary  Volume.  In  what  I  have  to  say  I  shall 
endeavor  to  study  conciseness  and  brevity: 

A  French  scientist  once  said,  "In  scientific  research  be  extremely 
careful  for  fear  you  may  find  exactly  what  you  are  looking  for." 
In  the  field  of  medicine  such  words  could  be  no  more  true,  either  in 
behalf  of  the  patient  who  may  enumerate  innumerable  symptoms, 
or  the  physician  who  consciously  or  unconsciously  observes  only 
the  apparent  symptoms.  How  often  the  internist  will  base  his  com- 
plete diagnosis  upon  a  complex  of  defensive  or  reactionary  symptoms 
and  avoid  or  even  neglect  the  actual  setting  of  those  signs,  especially 
so  with  regard  to  the  interrelation  or  linking  together  of  the  systemic 
organs,  either  through  the  nervous  system  or  through  the  vascular 
system,  with  its  vast  quantity  of  blood  and  its  complex  biochemical 
formulae  I 

Except  within  the  study  of  neuroses  and  psychoses  the  problem 
of  individuality  or  makeup  is  rarely  examined,  and  yet  without  it 
the  full  value  of  the  organic  or  even  functional  disorder  is  far  from 
complete.  Self-preservation  is  man's  uppermost  wish,  and  hence 
his  adaptative  mechanism  must  meet  fairly  and  squarely  not  only 
the  preservation  of  its  species,  but  also  its  social  attributes  and  their 
environmental  adjustment.   It  is  here  that  motive  and  conduct 

659 


66o  PERSONALITY  AND  DISEASE 

reaction,  with  either  its  corresponding  instinctive  demands  or  its 
emotional  evaluation,  largely  is  manifest,  offering  complex  settings 
and  transitory  as  well  as  variable  symptom-complexes.  Thus  one 
may  readily  observe  that  oftentimes  a  far  greater  number  of  symp- 
tom indicators  arise  from  origins  that  have  no  apparent  direct  rela- 
tion to  the  organ  involved,  and  develop  in  a  region  one  may  never 
suspect  disturbed.  It  has  always  been  the  tendency  to  take  man 
at  his  own  valuation,  and  then  to  assume  that  the  most  sure  way  of 
finding  out  how  such  and  such  a  symptom  developed  is  simply  to 
ask  him,  not  recognizing  the  fact  that  defensive  reactions  are  obsta- 
cles in  way  of  a  final  interpretation  as  well  as  a  recovery.  These 
defensive  reactions  serve  as  excitants  and  irritants  in  the  connecting 
chain  of  neuro-physical  and  neuro-psychical  components,  disturbing 
now  the  vegetative  mechanism,  again  an  emotional,  still  again  the 
instinctive,  adding  many  symptoms  quite  foreign  to  the  initial 
disturbance,  and  often  cloaking  the  actual  difficulty.  For  example: 
a  woman  of  forty  years  was  treated  for  hemorrhages  from  the  bowels, 
said  to  be  due  to  sclerosis  of  her  intestinal  vessels.  Sclerosis  imme- 
diately roused  an  emotional  activity,  and  environmental  maladjust- 
ment arose.  Her  behavior  towards  this  maladjustment  naturally 
took  on  an  apparent  preservative  coloring,  whereas  in  reality  her 
emotional  factors  and  her  instinctive  demands  in  turn  disturbed  her 
vegetative  system,  with  the  result  that  cardiac,  gastro-intestinal, 
and  general  vasomotor  symptoms  became  quite  obvious,  destructive 
rather  than  preservative.  Then,  again,  with  total  disregard  of  this 
growing  neuro-psychophysical  complex,  she  is  quietly  informed  and 
courageously  accepts  from  the  internist  the  statement  of  "non- 
compensating  chronic  heart."  (How  close  one  still  is  to  the  initial 
vascular  sclerosis.)  All  phenomena  are  now  involved,  body  and  mind, 
vegetative  system,  instinct,  emotion,  and  personality.  What  a  plight 
the  family,  as  well  as  the  patient,  now  face,  for  with  each  rise  or 
fall  in  the  threshold  of  feeling  in  the  patient  there  was  a  correspond- 
ing modification  in  the  emotional  and  instinctive  life  of  the  immedi- 
ate family. 

When  approached,  at  this  time,  by  the  psychopathologist,  who 
observed  the  entire  problem  from  the  standpoint  of  maladaptation 
towards  self  and  environment,  it  was  quite  obvious  that  the  initial 
hemorrhages  were  traumatic,  from  "marble"  stools  incident  to 


PERSONALITY  AND  DISEASE  66i 

spastic  constipation  of  autonomic  origin.  Hence  one  might  infer 
that  her  autonomic  system  was  "conditioned,"  and  probably  so 
determined  by  the  fact  that  her  makeup  for  years  prior  to  her 
primary  disorder  was  neuropathic  (vagotonic).  Conflicting,  emo- 
tional trends  broke  down  this  "conditioned"  system  and  added  more 
cardio-vascular  signs.  They  were,  however,  signs  of  vegetative 
disharmony,  a  loss  of  tone  rather  than  a  destruction  of  tone.  A  return 
to  society  was  soon  acquired  by  the  breaking  down  of  her  emotional 
defenses,  strengthening  her  instinctive  demands  and  readjusting  her 
vagus  tone. 

The  complexity  of  this  problem  is  far  reaching  and,  at  times, 
discouraging.  In  systemic  disease  processes  of  the  spinal  cord,  where 
toxic  substances  or  biochemical  changes  in  the  blood  are  utilized 
as  indicators  of  the  disease  and  its  activity,  due  consideration  should 
be  given  to  the  makeup  of  the  individual,  and  his  response  to  emo- 
tional stimuli  and  instinctive  demands,  before  relegating  some  of  his 
symptoms  to  the  pigeonhole  of  imagination.  It  may  not  be  a  surmise 
to  state  that  such  toxines  or  biochemical  phenomena  as  produce  the 
cord  lesion  might  produce  a  lesion  in  the  ganglionated  cord  of  the 
sympathetic  chain,  or  it  (the  toxine)  may  so  "condition"  the  auto- 
nomic system  as  to  select  the  organic  lesion.  The  personality  factor, 
the  behavioristic  response,  is  quite  manifest  in  syphilis  of  the  nervous 
system,  and  interest  should  lie  in  not  only  striving  for  a  cure,  but 
so  stabilizing  the  makeup  as  to  lessen  the  possibihties  of  late  syphilis 
manifesting  itself  in  personality  changes.  For  example:  a  man  with 
a  manic  makeup  developing  meningo-encephalitis  might,  presuma- 
bly, be  grandiose  in  his  psychic  sphere.  His  readjustment  should  not 
only  be  remedial  as  far  as  his  organic  process  is  concerned,  but  also 
his  "ego,"  his  self,  and  his  relation  to  society  require  adjustment. 
May  there  not  be  a  close  relation  between  the  disease  process  (histo- 
pathological)  and  the  personality  with  its  behavioristic  and  emo- 
tional components  (psychological)  in  such  a  case?  But  still  more 
marked  is  the  ever-present  fear  and  those  horrible  anticipatory 
imaginings  of  the  tabetic  and  his  pains.  Even  after,  treatment  with 
subsidence  of  the  actual  neuritic  pains,  should  a  non-tabetic  pain 
occur  the  pain-stimulus  undoubtedly  reproduces  in  kind  and  often 
in  degree  the  original  pain-stimulus.  The  emotional  experiences 
and  activities  in  these  patients  are  alert,  quick,  and  instantly 


662  PERSONALITY  AND  DISEASE 

responsive,  with  the  result  that  the  fear  probably  influences  the 
autonomic  system. 

There  are  patients,  also,  whose  autonomic  system  not  infrequently 
causes  a  phenomenon  not  unlike  intermittent  claudication.  For  ex- 
ample: a  man  of  fifty,  whose  makeup  was  quick  and  active,  whose 
emotion  was  swayed  by  the  rise  and  fall  of  luck,  and  one  whose  sex 
life  was  never  subjected  to  a  normal  control,  develops  at  forty-three 
the  tabetic  syndrome.  His  remorse  for  a  poorly  spent  sex  life  and 
his  regret  at  not  maintaining  an  economic  grip  upon  himself  led  to 
depressive  thoughts  and  later  physical  neglect.  Examination  not 
only  revealed  an  organic  disorder  of  the  tabetic  type,  but  also  a 
distinct  vegetative  disturbance  of  the  cardio-vascular  type  and  a 
modified  instinctive  reaction  with  emotional  instability.  Environ- 
ment might  exaggerate  one  or  all.  Specific  treatment  caused  the 
abatement  of  his  organic  subjective  symptoms.  Yet  with  this  much 
under  control  he  continued  in  morbid  fear  of  the  return  of  his  pains, 
and  whereas  primarily  the  anxiety  reaction  accompanied  the  organic 
reaction,  it  was  manifest  alone.  His  autonomic  difficulty  was  of  the 
sympatheticotonic  type,  and  treatment  directed  accordingly  at  the 
time  adjusted  that  phase.  There  still  remained  the  anxiety  dis- 
turbance and  his  modified  instinctive  demands.  Environmental 
adaptation  in  the  latter,  and  a  gradual  eradication  of  his  fear  with 
the  actual  disappearance  of  his  real  pains  and  the  creation  of  a 
dream-Hke  memory  of  those  true  pains,  the  patient  soon  became 
quite  comfortable  and  adjusted  himself  to  society.  It  would  appear 
that  the  patient's  cardio-vascular  system  was  "conditioned" 
through  an  autonomic  sensitization,  and  that  his  emotional  reaction 
was  brought  out  not  only  by  a  stimulus  which  did  not  originally 
call  it  up,  but  also  that  a  lingering  emotion  might  have  continued 
and  produced  recall  even  after  the  actual  subsidence  of  true 
symptoms. 

McDougall  states  that  the  idea  of  self  and  the  self-regarding 
sentiment  are  essentially  social  products,  that  their  development 
is  eff"ected  by  a  constant  interplay  between  personalities,  between 
self  and  society,  and  its  conception  must  be  always  of  one's  self 
in  relation  to  other  selves.  That  is,  one  must  often  give  up  pleasure- 
winning  ways  of  satisfying  one's  self  and  adapt  himself  to  any  new 
condition  arising.  This  self-sacrifice  may  bring  about  a  conflict 


PERSONALITY  AND  DISEASE  663 

between  the  pleasure-pain  and  reality  motives,  and  in  so  doing 
return  to  the  infantile,  with  a  complete  destruction  of  one's  ideal, 
and  maybe  a  progressive  separation  of  his  personality  from  the 
community  in  general.  In  the  compulsion  neuroses  there  is  a  regres- 
sion of  the  sex  craving  to  its  earlier  stage,  with  the  development  of 
an  CEdipus  mechanism. 

One  can  but  feel  the  great  value  of  this  mechanism  as  seen  in 
many  cases  of  so-called  "chronic  invalidism,"  especially  true  in  the 
fifth  and  sixth  decade  in  women.  It  usually  manifests  itself  at  the 
stage  of  menopause,  and  gradually  becomes  a  fixed  state  of  both 
mental  and  physical  destruction.  Since  all  love  has  as  its  funda- 
mental object  the  preservation  of  species,  either  in  self  or  through 
self,  then  that  failure  in  one's  eagerness  to  reach  an  ideal  may  not 
only  warp  the  personality  of  the  patient,  but  also  destroy  the  per- 
sonahty  of  the  child,  and  both  the  neurosis  in  the  former  and  the 
psychosis  in  the  latter  will  undoubtedly  take  on  the  OEdipus-incest 
complex  with  poor  chance  for  readjustment.  These  patients  fre- 
quently complain  for  years  of  vague  and  poorly  recognized  physical 
complaints  which  rather  often  symbolize  unsatisfied  cravings.  For 
instance,  one  young  man  has  tried  all  sorts  of  doctors,  quacks,  etc., 
to  obtain  a  permanent  removal  of  hair  from  his  face.  An  absence  of 
a  secondary  sex  character  would  enhance  his  feminine  characteristics 
and  complete  a  more  or  less  cloaked  female  conduct  reaction.  This 
young  man  was  left  at  two  years  of  age  with  his  mother  by  the 
sudden  death  of  the  father.  The  mother  brought  him  up  under  the 
most  strict  and  yet  good  environment.  They  schooled  together,  read 
together,  had  the  same  interests  in  music,  literature,  and  poetry. 
The  boy  became  proficient  in  music,  became  an  art  and  poetry 
critic,  and  worked  well  under  guidance.  When  he  reached  the  age  of 
fifteen  his  mother,  then  forty-seven,  had  an  accident,  and  evidently 
developed  a  "traumatic  spine,"  with  the  result  that  she  has  grown 
less  and  less  adaptable  to  herself  or  her  environment.  This  physical 
incapacity  upon  the  part  of  the  mother  caused  the  son  to  attach 
himself  more  strongly  to  his  mother,  and  both  gradually  became 
crippled  in  such  a  way  as  to  leave  them  inadequately  equipped  to 
deal  with  reality,  the  mother  frequently  enumerating  what  might 
have  resulted  "if"  such  and  such  a  thing  had  not  occurred,  and 
her  son  might  have  been  a  "big  chemist"  or  a  "poet  of  the  highest 


664  PERSONALITY  AND  DISEASE 

order"  if  such  a  thing  had  not  happened;  the  son  in  turn  emphasizing 
trivial  occurrences  and  indicating  his  regrets  accordingly.  At  this 
time  the  mother  is  an  invaHd,  with  gastro-intestinal  and  urinary 
disturbance,  the  former  manifest  by  spastic  constipation  and  peri- 
odical diarrheas,  and  the  latter  by  frequency  (organic  examination 
negative).  The  son  has  marked  insomnia,  indigestion,  and  "ner- 
vousness." 

Presumably  there  is  a  distinct  unconscious  conflict  related  to 
success  both  in  the  mind  of  the  mother  and  the  son.  Emancipation 
•of  the  son  has  not  taken  place.  The  mother  is  incapable  farther  of 
idealizing  in  reality.  Destruction  of  omnipotence  in  life  and  love  is 
an  admission  of  actual  loss  of  species  preservation.  Truthfully  to 
meet  the  reaction  would  mean  a  social  insult  of  a  severe  type.  To 
build  a  defense  reaction  means  to  separate  one's  self  from  his  social 
Hfe  with  the  complete  collapse  of  social  values,  and  a  substitution  in 
both  mental  and  physical  symptoms  of  such  psycho-sexual  activities 
as  conversion  of  the  all-powerfulness  of  thought  into  autoerotic  and 
incestuous  symbols. 

The  extent  to  which  investigations  into  personality  and  its 
relation  to  all  disease  process  is  of  value  can  be  reached  only  by 
making  such  an  examination  a  part  of  the  history  of  all  patients. 
Many  times  patients  are  treated  for  "local"  symptoms  when  their 
greatest  difficulty  is  their  makeup  and  its  adjustment.  Man  is  first 
of  all  a  social  animal,  and  the  struggling  desire  for  life's  existence  and 
for  a  rational  fulfillment  of  it  is  becoming  more  and  more  a  struggle 
between  self  from  a  psychological  viewpoint  and  society  from  its 
social  aspect,  and  from  such  he  must  be  so  considered  and  treated. 

Bergson  says,  "When  a  shell  bursts,  the  particular  way  it 
breaks  is  explained  both  by  the  explosive  force  of  the  powder 
it  contains  and  by  the  resistance  of  the  metal.  So  of  the  way  life 
breaks  into  individuals  and  species.  It  depends,  we  think,  on  two 
series  of  causes,  the  resistance  life  meets  from  inert  matter,  and  the 
explosive  force,  due  to  an  unstable  balance  of  tendencies  which  life 
bears  within  itself." 


MEDICAL  EXAMINATION  OF  MEN  FOR  MILITARY 
SERVICE:  SOME  OF  ITS  PROBLEMS,  LESSONS 
AND   RESULTS 

By  Sir  James  Galloway,  K.B.E.,  C.B.,  M.D.,  LL.D.  (Aberd.), 
F.R.CS.  (Eng.),  F.R.CP.  (Lond.) 

Chief  Commissioner  of  Medical  Services,  Ministry  of  National  Service;  Colonel,  Army 

Medical  Service;  late  Consulting  Physician  I.  and  II.  Armies,  B.  E.  F.;  Senior 

Physician,  Charing  Cross  Hospital 

IN  Other  circumstances  it  would  have  been  the  wish  of  the  writer 
to  contribute  a  paper  giving  the  result  of  clinical  observation, 
as  an  expression  of  regard  to  an  acknowledged  master  of  clinical 
medicine,  but  my  old  Chief  well  knows  the  urgent  circumstances  that 
for  a  period  of  time  obliged  me  to  relinquish  my  work  as  a  clinician 
in  order  to  undertake  duties  involving  direction  of,  rather  than  per- 
sonal participation  in,  medical  practice. 

I  hope  that  the  following  account  of  some  of  the  more  directly 
medical  aspects  of  the  work  done  may  not  be  devoid  of  interest. 

Before  the  Great  War  the  medical  examination  of  recruits  for 
the  army  was  carried  out  by  medical  officers,  retired  or  on  the 
active  hst,  and  by  civilian  medical  practitioners.  The  standard  used 
was  that  laid  down  in  Army  Medical  Service  Regulations,  and  the 
men  were  passed  as  "fit"  or  "unfit."  No  attempt  was  made  to 
place  them  in  grades  or  categories.  This  system  did  not  lend  itself 
to  accurate  investigation  and  record  of  the  physical  condition  of  the 
men,  and  gave  partial  and  misleading  information  as  to  the  health 
and  physical  state  of  the  population. 

At  the  beginning  of  the  war,  when  the  first  great  voluntary 
rush  to  the  colours  was  witnessed,  the  same  system  of  recruiting  was 
pursued,  but  under  new  and  greatly  increased  difficulty,  owing  to 
urgent  pressure  of  time  and  want  of  suitable  accommodation  for 
medical  inspection. 

On  October  20,  191 5,  the  scheme  of  recruiting  associated  with  the 
name  of  Lord  Derby  came  into  operation  and  caused  a  further  great 
flocking  of  recruits  to  the  colours.  The  medical  examination  of  these 

665 


666         EXAMINATION  FOR  MILITARY  SERVICE 

men,  which  was  carried  out  under  great  difficulties,  caused  so  much 
unfavourable  public  criticism  that  the  War  Office  made  a  complete 
change  in  the  procedure  of  medical  examination.  Fortunately  for  the 
country,  the  medical  administration  of  the  War  Department  at 
home  was  then  in  the  hands  of  Sir  Alfred  Keogh. 

On  December  24,  19 15,  the  War  Office  ordered  the  formation 
of  Medical  Boards  to  replace  the  system  of  examination  by  single 
medical  officials  previously  in  practice.  These  boards  were  designed 
to  consist  of  a  president  and  three  or  four  members.  The  examining 
members  in  many  cases  were  civilians,  but  the  president  of  the 
board  was  a  military  medical  officer,  usually  holding  the  rank  of 
Lieutenant-Colonel  or  Major.  In  a  few  cases  these  officers  were  still 
on  the  active  hst,  but  usually  they  had  retired  from  the  army  be- 
fore the  war. 

These  boards  were  instructed  to  place  the  recruits  in  categories. 
The  first  Army  Council  Instruction  dealing  with  this  important 
matter  was  issued  in  January,  19 16,  and  laid  down  the  following 
categories  of  fitness: 

1.  For  general  service. 

2.  For  field  service  at  home. 

3.  For  garrison  service,  (a)  abroad,  (6)  at  home. 

4.  For  (a)  labour  (road  making,  entrenching  work,  etc.) 
For  (6)  sedentary  work  (clerks,  etc.) 

It  was  expected  that  each  board  should  be  able  to  examine  200 
men  daily. 

It  will  be  noted  that  even  at  this  date  the  system  of  categorisation 
involved  two  conceptions:  the  first  derived  from  purely  medical 
data — the  man's  physical  condition  and  state  of  health  at  the  time  of 
examination;  the  second  involving  administrative  considerations, 
indicating  the  form  of  service  for  which  he  was  presumed  to  be  fitted 
on  entering  the  army.  The  task  of  combining  these  two  ideas  was  one 
of  the  main  difficulties  to  be  faced  by  the  boards,  most  of  whom 
were  largely  civilian  in  composition;  this  difficulty  increased  as  time 
went  on  until  in  191 7  the  attempt  had  to  be  abandoned.  The 
attempt  to  solve  the  problem  at  one  decision  of  the  board  gave  rise 
to  much  confusion,  and  ultimately  much  unrest  in  the  minds  of  the 
public — a  trouble  that  was  never  satisfactorily  dispelled. 

In  April,   19 16,  a  classification  certificate  was  issued  for  the 


EXAMINATION  FOR  MILITARY  SERVICE        667 

first  time  to  men  who  had  been  medically  examined.  This  document 
became  of  much  importance  in  the  recruiting  system  and  developed 
ultimately  into  the  grade  card  of  the  Ministry  of  National  Service. 
On  May  19,  1916,  Army  Council  Instruction  1023  was  issued, 
which  divided  men  into  five  categories: 

(A)  Fit  for  general  service. 

(B)  Fit  for  service  abroad. 

(C)  For  service  at  home  only. 

(D)  Temporarily  unfit  for  service  in  A,  B,  C,  but  likely  to  become 

fit  in  six  months,  and  meanwhile  either 

(E)  Unfit  for  service  in  A,  B,  C,  and  not  likely  to  become  fit 

in  six  months;  or  awaiting  discharge  or  reclassification. 

Classes  A,  B,  C,  and  D  were  further  subdivided  into  three 
categories. 

This  Army  Council  Instruction  was  for  use  not  only  by  Recruit- 
ing Medical  Boards,  but  also  by  regimental  officers  and  all  others 
within  the  army.  There  were  at  least  thirteen  categories  in  which 
men  could  be  placed.  These  details  are  given  to  show  how  completely 
classification  to  aid  administrative  requirements  overshadowed 
classification  on  purely  medical  grounds. 

During  1916  recruiting,  which  had  now  become  compulsory  for 
certain  sections  of  the  adult  male  population,  was  carried  on  more 
intensively,  owing  to  the  ever  increasing  demands  for  men.  As  an 
inevitable  result,  the  recruiting  machinery  and  methods  came  under 
pubHc  criticism.  It  is  in  the  medical  board  and  at  the  hands  of  the 
medical  men  working  on  these  boards  that  the  recruit  first  feels  the 
actual  touch  of  compulsory  military  service — his  medical  examina- 
tion is  his  initiation  into  mihtary  methods.  It  is  only  to  be  expected, 
therefore,  that  the  public  will  watch  critically  the  methods  employed 
by  the  boards  and  examining  medical  officers.  The  medical  boards — 
their  medical  administration  and  organisation — had  to  bear  the 
brunt  of  this  criticism,  much  of  it  badly  informed  and  far  from 
helpful,  much  of  it  influenced  by  political  prejudice.  Later  the 
administration  of  recruiting  under  the  Mihtary  Service  Acts  was 
given  over  to  a  special  department  of  the  War  Office  and  placed 
under  the  control  of  Brigadier-General,  now  Sir,  Auckland  Geddes. 

At  the  end  of  19 16  it  was  found  necessary  to  institute  more 
close  supervision  of  the  medical  boards  with  a  view  to  reorganisa- 


668         EXAMINATION  FOR  MILITARY  SERVICE 

tion,  and  a  special  medical  department  was  formed  to  undertake 
this  work. 

In  December,  191 6,  and  early  in  19 17,  the  writer  inspected  nearly 
every  recruiting  centre  throughout  the  country  in  order  to  obtain 
information  as  to  the  methods  used  and  the  quality  of  the  medical 
work.  It  was  manifestly  clear  that  as  the  war  progressed  recruiting 
would  bear  still  more  hardly  on  the  population,  interfering  more  and 
more  with  trades  and  occupations,  until  at  length  only  the  essential 
industries  could  be  permitted  to  continue.  With  this  prospect  in 
view,  it  became  necessary  to  arrange  the  medical  machinery  to  be 
not  only  efficient,  but  to  give  as  little  offence  as  possible.  The  days  of 
voluntary  recruiting  had  passed;  recruiting  and  medical  examination 
now  concerned  every  effective  man  in  the  community. 

Reorganisation  was  brought  about  just  in  time,  for  on  April  5, 
191 7,  the  Military  Service  (Review  of  Exceptions)  Act  came  into 
operation.  This  Act  provided  for  the  calling  up  for  medical  examina- 
tion of  large  numbers  of  men  who  had  previously  been  excepted 
from  the  operation  of  the  Military  Service  Acts.  It  will  be  remem- 
bered how  difficult  it  was  to  put  the  provisions  of  this  Act  into 
operation  and  how  in  course  of  time  the  operation  of  the  Act  produced 
acute  political  disturbance.  The  intensity  of  feeling  against  the 
operation  of  the  Act  manifested  itself  largely  by  embittered  criticism 
of  the  working  of  the  medical  organisation  of  the  Recruiting  Depart- 
ment of  the  army.  After  an  anxious  period  marked  by  much  dis- 
turbance, a  Select  Committee  of  the  House  of  Commons  was 
established  to  enquire  into  the  administration  of  the  Act,  which 
made  the  following  amongst  other  recommendations: 

"The  Committee  recommends  that  the  whole  organisation  of  Recruit- 
ing Medical  Boards  and  of  the  medical  examinations  and  re-examinations 
should  be  removed  from  the  War  Office  and  placed  under  civilian  control." 

In  consequence  of  this  recommendation  Sir  Auckland  Geddes  was 
appointed  Minister  of  National  Service,  and  the  previously  existing 
Department  was  thoroughly  reconstituted.  The  Recruiting  Depart- 
ment of  the  Adjutant-General's  Office,  including  the  Medical  Sec- 
tion, was  transferred  to  the  Ministry  of  National  Service,  and 
henceforth  recruiting  for  the  army  with  all  its  medical  organisation 
passed  into  what  proved  to  be  the  last  stage  of  development.  After 


EXAMINATION  FOR  MILITARY  SERVICE         669 

a  strenuous  period  of  preparation  the  reconstituted  Ministry  of 
National  Service  commenced  as  from  midnight,  October  31,  19 17. 

During  the  year  19 16  the  experience  gained  of  the  work  of 
recruiting  medical  boards  under  the  army  had  been  gradually 
collated,  with  the  result  that  during  this  year  the  organisation, 
the  personnel,  and  administrative  methods  of  the  boards  underwent 
a  gradual  change.  In  the  latter  part  of  the  summer  the  boards  had 
gradually  been  placed  on  a  new  basis,  so  that  when  the  great 
change  took  place  from  military  to  civihan  administration,  no 
noticeable  jar  to  the  machinery  occurred.  The  organisation  and  ad- 
ministration proceeded  on  the  methods  which  had  been  previously 
thought  out,  and  which  had  now  the  opportunity  of  becoming  fully 
developed. 

It  had  become  increasingly  obvious  that  the  attempt  to  super- 
impose a  classification  adapted  to  assist  the  administrative  side  of 
the  army  on  work  done  by  medical  boards,  now  largely  civilian, 
could  not  be  continued,  both  for  reasons  of  efficiency  and  on  account 
of  the  social  and  political  difficulties  which  such  a  method  of  classifi- 
cation inevitably  brought  in  its  train.  The  old  army  categories  were 
guides  to  posting  officers,  based  only  partly  on  the  result  of  medical 
examination.  Classification  of  a  man  in  one  of  the  existing  categories 
was  therefore  clearly  the  function  of  the  army,  and  not  of  a  board  of 
a  civilian  ministry. 

It  was  necessary  for  the  new  recruiting  organisation  to  establish 
certain  broad  principles  of  classification  of  the  men  supplied  to 
the  army,  for  it  would  be  useless  to  supply  1000  men  fit  only  for 
employment  as  clerks  when  the  demands  of  the  army  were  for  1000 
fighting  men.  Classification  was  therefore  essential,  but  the  medical 
and  administrative  aspects  of  the  classification  had  to  be  sharply 
difi'erentiated — relegated  to  civilian  medical  boards  on  the  one  hand, 
and  to  the  military  medical  organisation  within  the  army  on  the 
other. 

Experience  had  shown  that  men  of  military  age  can  be  classified 
by  medical  examination  into  four  great  groups,  determined  by 
physical  considerations  alone: 

I .  Men  free  from  serious  defects  or  organic  disease,  of  good  muscular 
development,  actual  or  potential,  the  movements  of  their  joints  unimpaired, 
their  special  senses  acute,  of  good  intelligence  and  at  the  time  of  being 


670         EXAMINATION  FOR  MILITARY  SERVICE 

handed  over  to  the  army,  free  from  such  infectious  and  contagious  dis- 
eases as  are  not  transient  or  rapidly  curable. 

2.  Men  fulfilling  the  above  conditions,  but  whose  special  senses, 
e.g.,  eyesight — may  be  below  the  normal  standard,  but  nevertheless  suffi- 
ciently good  for  all  ordinary  purposes.  Men  in  these  two  groups  are  capable 
of  active  service. 

3.  Men  with  defects  which  do  not  interfere  with  their  vocation  in 
civil  life  or  with  organic  disease  not  likely  to  be  incapacitating  for  a 
considerable  period  of  years.  These  men  must  possess  fair  intelligence  and 
be  able  to  perform  the  duties  allotted  to  them  regularly.  Men  in  this 
group  are  required  to  perform  the  multifarious  auxiliary  services  required 
for  a  modern  army. 

4.  Men  whose  defects  or  disabilities,  physical  or  mental,  are  of  such  a 
nature  or  of  so  severe  a  degree  as  to  render  them  unfit  for  service  in  the 
army. 

It  was  on  these  considerations  that  the  four  well-known  grades 
of  the  National  Service  Medical  Boards  were  established,  and  from 
the  time  that  the  National  Service  Ministry  undertook  medical 
examination  for  recruiting  the  grading  of  men  was  carried  out  on  the 
principles  indicated. 

During  this  period  of  reconstruction  the  actual  organisation  of 
the  boards  themselves  had  undergone  changes.  The  fully  developed 
National  Service  Medical  Board  consisted  of  a  president  and  four 
members.  The  examination  of  the  men  was  conducted  on  a  sectional 
method.  Experience  had  shown  that  the  best  results  in  medical 
examination  from  the  point  of  view  both  of  accuracy  and  of  standard 
results  were  obtained  if  the  candidate  was  examined  by  the  members 
of  the  board  in  turn,  each  examiner  in  addition  to  a  general  view 
of  the  recruit  paying  attention  especially  to  certain  sections  of  the 
examination.  The  president  of  the  board  co-ordinated  the  work  of 
the  examiners,  collated  the  results  in  every  case,  arranged  for  more 
formal  consultation  of  examiners  in  difficult  cases,  and  always 
pronounced  the  final  grading  of  the  recruit.  The  methods  of  the 
National  Service  Medical  Boards  are  given  fully  in  the  instruction 
which  was  issued  at  the  commencement  of  the  work  of  the  Min- 
istry, the  last  edition  of  which  was  published  in  December,  19 18 
(M.N.S.R.,  88). 

The  National  Service  Medical  Boards,  constituted  on  this  basis 
and  composed  of  the  best  available  practitioners  left  in  the  country. 


EXAMINATION  FOR  MILITARY  SERVICE         671 

by  degrees  developed  into  a  very  efficient  organisation  for  the 
estimation  of  physical  fitness.  The  quality  of  their  work  naturally 
improved  with  time,  and  now  the  members  of  these  boards,  to  the 
number  of  3000  to  4000,  have  acquired  special  knowledge  of  methods 
of  examination,  of  the  conditions  underlying  physical  fitness,  and 
aptitude  in  the  recognition  of  what  makes  a  man  fit  or  unfit  which 
will  be  of  great  service  to  the  State  in  the  future.  The  work  reacted 
beneficially  on  the  profession  itself;  it  brought  medical  colleagues 
together  in  all  parts  of  the  country;  they  worked  together,  and  got 
to  know  each  other  well.  The  work  developed  in  some  respects  in 
the  nature  of  a  post-graduate  course  of  training.  These  good  results 
were  much  appreciated  and  favourable  opinions  were  expressed  to 
the  writer  on  many  occasions. 

To  give  an  indication  of  the  work  done,  it  may  be  stated  that 
from  November,  i,  19 17,  to  October  31,  191 8,  2,425,184  medical 
examinations  were  carried  out  by  the  boards;  in  May  the  numbers 
reached  456,599,  and  in  June,  475,416. 

The  Development  of  a  Standard  for  Estimating  the  Fitness  of 
Groups  oj  Men.  At  an  early  stage  of  the  work,  before  the  boards 
developed  their  final  phase,  it  became  clear  that  there  was  an  op)- 
portunity  of  obtaining  an  intimate  knowledge  of  the  health  of  the 
community,  especially  of  the  conditions  producing  deviations  from 
the  normal,  degeneration,  and  disease,  and  particularly  the  eff"ects 
of  the  habits  and  occupations  of  the  people. 

It  soon  became  desirable  to  obtain  an  index  of  the  condition  of 
groups  of  the  population  as  compared  with  what  might  be  consid- 
ered the  normal  standard.  After  some  consideration,  the  following 
rough  indication  was  arrived  at,  and  has  proved  to  be  a  serviceable 
guide. 

The  suggestion  as  to  the  method  of  obtaining  such  an  index 
is  due  to  Professor  Arthur  Keith,  of  the  Royal  College  of  Surgeons. 
Taking  the  results  of  the  medical  examination  of  1000  young  men 
who  may  fairly  be  considered  to  have  been  reared  under  good 
conditions,  it  was  found  that  seven  companies  of  100  men  should  be 
in  Grade  I;  two  companies  in  Grade  II;  and  of  the  remaining 
company  of  100,  three  platoons  of  25  in  Grade  III,  and  one  platoon 
of  25  in  Grade  IV.  In  other  words,  1000  young  men  drawn  from  a 
normally   healthy   section   of  the  population  should  yield  seven 


672         EXAMINATION  FOR  MILITARY  SERVICE 

companies  of  Grade  I  men;  two  companies  of  Grade  II;  three- 
fourths  of  a  company  of  Grade  III,  and  one-fourth  of  a  company  of 
Grade  IV.  Quoting  Professor  Keith's  words  in  a  very  helpful  letter 
addressed  to  the  writer: 

"We  cannot  get  a  better  method  of  giving  a  concrete  expression  to  the 
degree  of  fitness  than  that,  yet  the  method  is  too  clumsy  for  ready  use. 
We  need  a  more  concise  method  of  estimating  and  expressing  the  degree  of 
fitness — a  figure  which  will  give  us  the  relative  degree  of  fitness  in  any  batch 
of  men  examined  by  a  medical  board.  The  method  I  would  propose  is  one 
used  in  anthropological  work.  Let  us  suppose  the  board  has  just  examined 
1000  men  with  the  following  result: 

700  are  placed  in  Grade     I. 
200  are  placed  in  Grade    II. 

75  are  placed  in  Grade  III. 

25  are  placed  in  Grade  IV. 

Each  Grade  I  man  has  his  full  unit  of  fitness 700       units 

Each  Grade  II  man  we  will  assess  at  ^,  or  75  per  cent  of  a 

unit.  The  200  men  have  amongst  them  200  x  ^.  .  .  .  150        units 

Each  Grade  III  man,  assessed  at  ^  unit,  gives  us  75  x  ^. .  37.5     units 

Each  Grade  IV  man,  assessed  at  ^  unit,  gives  us  25  x  -j- . . .  6 .  25  units 


893 -75 

That  is  to  say,  in  this  artificial  but  yet  approximately  accurate  method, 
the  battalion  of  men  just  examined  had  893.75  units  of  fitness — or  cutting 
the  expression  short — the  amount  of  fitness  was  89.375  per  cent  of  the 
total  possible.  The  index  of  fitness  of  that  group  of  men  may  be  expressed 
as  89.3." 

This  index,  which  we  speak  of  as  "Keith's  index,"  has  been 
employed  from  time  to  time  in  our  work,  and  has  proved  useful  in 
forming  an  estimate  of  the  relative  value  of  man-power  in  different 
parts  of  the  country  and  in  different  groups  of  the  population. 

For  instance,  the  following  table  gives  an  idea  of  the  quality 
of  the  men  obtained  for  military  service  in  a  large  section  of  the 
country,  including  populations  occupied  in  agricultural  pursuits,  in 
mining,  in  the  steel  and  iron  trades,  and  in  textile  factories. 

Example  oj  Wide  Divergence  in  Physique  of  Population  in  Neigb^ 
bouring  Areas.  Extract  from  the  report  of  a  National  Service  visitor 


EXAMINATION  FOR  MILITARY  SERVICE 


673 


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d 

674         EXAMINATION  FOR  MILITARY  SERVICE 

after  visitation  of  Emergency  Boards  in  a  manufacturing  area  to 
enquire  into  the  reason  for  the  relatively  high  percentage  of  men 
placed  in  Grade  III: 

(A)  Emergency  Board,  dealing  with  recruiting  of  colliers.  April  5,  6, 
8  and  9,  1918;  412  men  examined  and  graded. 

Grade  I  II  III  IV 

319  39  50  3 

77.4%  9.4%  12.1%  .9% 

(B)  Emergency  Board,  dealing  with  the  recruiting  of  colliers.  April 
5,  6,  8,  and  9,  1918;  306  men  examined  and  graded. 

Grade  I  II  III  IV 

221  53  25  7 

72%  17.3%  8.1%  2.2% 

(C)  Emergency  Board,  dealing  with  munition  area  reserved  occupa- 
tions and  colhers.  April  5,  6,  8,  and  9,  1918;  314  men  examined  and  graded. 

Grade  I  II  III  IV 

257  27  29  I 

81.8%  8.5%  9-2%  .3% 

Combined  average  gradings  of  all  Emergency  Boards  in  this  region 
dealing  with  this  class  of  men,  mainly  colliers: 

Grade  I  II  III  IV 

70.6%  12.4%  13.2%  3.4% 

(D),  (E)  Emergency  Boards  dealt  with  cotton  operatives,  weavers 
and  spinners,  working  in  factories  instead  of  colliers  and  munition  area 
reserved  occupations.  The  population  examined  was  in  a  neighbouring 
portion  of  the  country  to  the  areas  dealt  with  by  Boards  A,  B,  and  C. 

The  visitor  remarks: 

"The  difference  is  marked  even  in  the  waiting  room,  and  becomes 
striking  in  the  examination  hall.  Age  for  age  the  colliers  strip  much  better 
than  the  cotton-mill  operatives,  and  are  as  a  class  muscular  and  well 
developed.  The  difference  is  revealed  in  a  more  exact  manner  by  the 
returns." 

(D)  Emergency  Board.  During  March,  1918,  40.95  per  cent  of  the  men 
examined  were  placed  in  Grade  III  and  16.8  per  cent  in  Grade  IV; 
combined,  57.5  per  cent.  During  April  5,  6,  8  and  9,  191 8,  184  men  were 
examined  and  graded  and  106  postponed,  as  the  Deputy  Commissioner 
of  Medical  Services  considered  they  would  obviously  fall  within  Grades 
III  and  IV. 


EXAMINATION  FOR  MILITARY  SERVICE 


675 


The  184  examined  and  graded  were  distributed  as  follows: 
Grade  I  II  III  IV 

57  64  56  7 

30.9%  34.7%  30.1%  3-8% 

If  the  106  cases  postponed,  presumed  to  be  Grades  III  or  IV,  are 
added,  we  get  the  following  figures: 

Grade  I  II  III  IV 

57  64  169 

19.6%  22%  58.2% 

The  visitor  records  his  opinion  that  the  grading  by  the  board 
was  in  general  correct,  and  adds  that  the  Deputy  Commissioner  of 
Medical  Services  is  of  opinion  that  work  in  the  moist  and  overheated 
atmosphere  of  the  cotton  mills  has  a  profound  eflFect  upon  the 
physique  and  health  of  the  operatives  when  extended  over  long 
periods,  so  that  they  age  quickly. 

(E)  Emergency  Board.  During  the  month  of  March,  191 8,  the  men 
examined  by  this  board  consisted  almost  entirely  of  cotton-mill  operatives, 
and  the  returns  show  a  daily  average  of  51.35  per  cent  of  Grade  III  and 
8.5  per  cent  of  Grade  IV.  Daily  combined  average,  59.85  per  cent. 

On  April  5,  6,  8  and  9,  19 18,  there  was  a  considerable  admixture  of 
colliers — 126  were  examined  and  graded. 

Grade  I  II  III  IV 

53  27  36  ID 

42%  21%  28.5%  7.9% 

These  figures,  though  eminently  unsatisfactory  when  compared 
with  the  returns  of  a  purely  miner  "comb-out,"  give  a  percentage 
of  36.4  per  cent  of  Grade  III  and  IV  men,  as  compared  with  the 
59.85  per  cent  of  the  cotton  operatives  in  the  previous  month. 

For  purposes  of  comparison  the  following  table  is  added : 

TABLE  II 


Grade  I 

Grade  II 

Grade  III 

Grade  IV 

Combined  average  gradin^s  of  boards 
examining    mainly    colliers    in    the 
region 

706 

12-4 

13. 2 

3.4=16-6 

Combined  average  grading  of  all  men 
examined  throughout  a  wide  area  of 
the  country  in  April,  1918 

55-9 

19. 8 

19. 2 

5. 1  =  24-3 

Grading  of  290  cotton  operatives  ex- 
amined by  Board  D,  on  April  5th, 
6th,  8th  and  9th 

19-6 

22 

58. 2 

676         EXAMINATION  FOR  MILITARY  SERVICE 

A  medical  official  in  this  area  made  the  following  commentary: 

"The  average  man  is  an  old  man  before  he  reaches  the  age  of  forty. 
.  .  .  The  folk  of  his  part  of  the  country  are  hardworking  and  industrious, 
and  from  an  early  age  absorbed  in  industry;  youths  on  being  questioned 
frequently  say  they  have  no  time  for  any  games;  they  begin  work  young, 
work  long  hours,  and  too  often  think  they  are  fully  compensated  if  they 
make  big  wages.  Thus  the  growing  boy  gets  no  chance  of  healthy  outdoor 
exercise  to  develop  his  frame — he  is  too  tired  at  the  end  of  a  hard  day's 
work  to  trouble  about  physical  culture.  He  is  not  troubled  by  his  physical 
condition,  he  accepts  it  with  dull  contentment — after  all  he  is  only  like 
his  fellows.  He  works  in  a  mill  which  has  to  be  kept  at  a  high  temperature. 
He  comes  out  in  the  evening  weary,  heated,  and  debilitated.  The  climate 
is  damp  and  cold,  he  readily  contracts  rheumatic  and  bronchitic  affections. 
Rheumatism  affects  his  heart;  hernia  is  easily  produced  when  the  muscles 
are  poor  and  flabby,  especially  when  there  is  frequent  cough  or  when  the 
work  is  really  beyond  his  strength.  Varix  and  fiat  foot  are  natural  results 
of  long  hours  of  standing,  when  the  muscles  are  flabby,  anaemic,  and 
weary. " 

Report  upon  Condition  of  2gg4  Men  between  Forty-three  and  Fifty- 
one  YearSt  Examined  in  Neighbouring  Areas  of  Boards  D  and  E. 
The  following  table  is  of  interest,  as  it  indicates  the  physical  state  of 
a  number  of  the  older  men  examined  in  areas  in  which  the  population 
is  employed  in  work  of  practically  the  same  nature  as  in  the  areas 
of  Boards  D  and  E.  All  these  areas  are  in  the  same  part  of  the 

country. 

TABLE  III 


Diseased  Conditions                               |    Number    |    Per  Cent 

Varicose  veins.                                                                                  |         602         |         29 

2 

Heart  affections.                                                                              |         462         |         15 

5 

Hernia.                                                                                               j         374         |         12 

5 

Rheumatic  affections.                                                                     |         315         |         10 

5 

Deformed  toes.                                                                                 |         308         |         10 

3 

Emphysema  and  bronchitis.                                                          I         268         |           8 

9 

Varicocele.                                                                                         |         234         |           7 

8 

Haemorrhoids.                                                                                            235         |           7 

8 

Deafness  and  otitis.                                                                                 214         |           7 

2 

Flat  feet.                                                                                                172         |           5 

8 

Arterial  degeneration.                                                                              124         |           4 

2 

No  disability  of  any  kind  noted.                                                                          |           8 

The  preceding  report  throws  light  on  the  effect  of  occupation  on 
the  physique  of  a  population  inhabiting  a  well-defined  section.  The 


EXAMINATION  FOR  MILITARY  SERVICE 


677 


reports  that  follow  reflect  the  influence  of  race,  environment,  and 
occupation  on  the  physique  of  a  definite  group.  The  statistics  of  the 
examination  of  aliens  are  derived  from  boards  in  London. 


TABLE  IV 

Causes  of  Rejection  among  Aliens  of  Jewish  Race  Examined  in  London  between 
September  20  and  November,  1917,  with  Corresponding  Figures  from 
Scotland. 


Race 

Number 
Examined 

Rejected 

Percentage 
Rejected 

Percentage  Rejected  for 
Pulmonary  Tuberculosis 

Russian  Jews. 

495 

135 

27-2 

91  Add  to  the  135  re- 
jected 23  relegated 
to  the  reserve,  dis- 
ability not  stated, 
158,  or  32.1  per 
cent. 

Scots. 

10,000 

440 

4-4 

11 

Details  of  Causes  of  Rejection 


Pulmonary  tuberculosis 45 

Valvular  disease  of  the  heart . .     17 

Bronchitis 12 

Trachoma 8 

Disease  not  stated 7 

Disordered  action  of  the  heart       5 

Emphysema 4 

Epilepsy 4 

Poor  physique 2 

Defective  vision 3 

Mentally  defective 3 

Albuminuria 2 

Duodenal  ulcer 2 

Varicose  veins 2 

Sycosis 

Ascites 

Curvature  of  spine 

Nasal  caries 

Gunshot  wound  head  and  leg. 

Otorrhoea 

Scar  after  appendicitis 

Fracture  right  leg 

Deafness 


Chronic  mediastinitis . . 

Glaucoma 

Disseminated  sclerosis . 
Rheumatoid  arthritis . . , 

Corneal  nebula 

Kyphosis 

Withered  right  arm . .  .  . 
Oto-sclerosis,  incurable. 

Old  choroiditis 

Sciatica 


135 
Relegated  to  reserve  (disability 
not  stated) 23 

158 
Ages. 

Between  18-25 24 

Between  26-30 30 

Between  31-35 35 

Between  36-41 46 

135 


678 


EXAMINATION  FOR  MILITARY  SERVICE 


TABLE  V 

Comparative  Frequency  of  Common  Disabilities  in  1100  British  and  1370 
Aliens  of  Jewish  Race,  London 


Disability 

Percentage  among 
British 

Percentage  among 
Russian  Jews 

Pulmonary  tuberculosis. 

2 

1 

19 

2 

Other  diseases  of  lungs. 

5 

0 

13 

5 

Eye  diseases. 

7 

7 

.9 

Ear  diseases. 

3 

2 

7 

3 

Diseases  of  throat  and  nose. 

2 

1 

6 

6 

Diseases  of  heart. 

12 

3 

14 

9 

Mental  diseases. 

4 

4 

Gastric  diseases. 

2 

1 

4 

4 

Syphilis. 

1 

1 

2 

0 

Gonorrhoea. 

6 

2 

0 

Epilepsy. 

3 

1 

4 

Obesity. 

9 

5 

3 

5  feet  6  inches  and  under. 

44 

9 

77 

8 

Defective  feet. 

12 

2 

24 

7 

Defective  teeth. 

22 

8 

21 

0 

Illiterates. 

2 

37 

1 

TABLE  VI 

Percentage  of  Grading  of  British  Yoxtths  of  Eighteen  and  Aliens  of  Jewish 
Race  Respectively,  London 

Grade                     1                 British                 |           Russian  Jews 

I                           1                     72-1                     j                     67-S 

II                           1                      151                      1                      162 

III                           i                        7-2                      1                      ICO 

IV                   1                 2.5               1                 3.8 

Deferred                    |                       3-1                     |                       2-5 

The  Deputy  Commissioner  of  Medical  Services  reports  as  fol- 
lows on  the  above  table: 

"Two  thousand  British  youths  were  examined  and  eighty  Russian 
Jews  of  this  age — no  more  appeared  for  examination  at  this  date.  They 
were  all  born  in  the  Russian  Ghettos,  nearly  all  of  German  extraction, 
brought  to  England  in  early  life  and  passed  through  our  schools. 

"On  these  figures  their  grading  corresponds  very  closely  to  that  of 
the  British  youths,  and  presents  a  very  marked  difference  to  that  of 
adult  Russian  Jews;  the  inference  appears  to  be  that  the  Russian  Jew 
deteriorates  and  becomes  diseased  chiefly  during  early  manhood." 

The  above  description  and  notes  partly  explain  the  way  in  which 
the  work  was  done  and  give  some  indication  of  the  results  obtained. 


I 


EXAMINATION  FOR  MILITARY  SERVICE         679 

The  writer  acknowledges  the  arduous  service  and  good  work  of  his 
colleagues  and  assistants. 

For  many  years  it  has  been  the  wish  of  those  interested  in  social 
and  racial  progress  to  have  a  mass  of  information  based  on  sufficiently 
accurate  observations  to  estimate  the  physical  condition  of  the  people 
at  the  time,  and  to  serve  as  a  datum  line  from  which  progress  or 
retrogression  in  the  future  could  be  judged.  More  than  one  effort 
has  been  made  to  study  the  problems  influencing  the  health  of  the 
people,  but  have  been  fruitless  because  sufficiently  accurate  data 
have  hitherto  been  wanting.  There  is  now  available  much  informa- 
tion giving  many  of  the  data  required,  some  of  which  is  now  in  the 
process  of  analysis  and  collation. 

In  addition  to  information  concerning  the  men  of  military  age, 
facts  are  being  collected  by  degrees  from  various  sources  respecting 
the  health  of  infants,  children,  young  persons  of  school  age,  and 
women.  The  opportunity,  therefore,  is  at  hand  for  making  an 
extensive  medical  survey  of  the  population,  but  in  order  to  make 
the  foundations  for  future  opinions  complete  and  firm,  arrangements 
must  be  made  to  obtain  information  comparable  to  that  obtained 
respecting  the  adult  population  of  military  age  during  the  past  four 
years.  The  state  of  our  manhood  at  the  beginning  of  life's  work 
should  be  under  survey  continuously,  and  at  intervals  thereafter 
the  state  of  the  population  should  be  investigated.  It  is  only  by 
methods  such  as  these  that  matters  of  such  vital  importance  as  the 
effects  of  occupation  on  our  workers  of  all  classes  and  the  results  of 
measures  intended  to  improve  the  public  health  can  be  estimated. 
Without  this  information,  plans  for  the  improvement  of  our  racial 
stock  will  be  badly  made  and  progress  must  be  at  random.  The 
medical  profession,  now  awakening  to  the  sense  of  its  responsibility 
for  the  health  of  the  community  and  not  merely  for  the  ill-health 
of  the  individual,  must  obtain  information  of  such  importance. 
But  the  signs  of  the  times  indicate  that  now  is  the  opportunity  to 
secure  what  we  require.  Let  us  not  forget  the  words  of  a  very  wise 
and  friendly  adviser: 

"Dimidium  facti  qui  coepit  habet;  sapere  aude: 
incipe:  qui  recte  vivendi  prorogat  horam, 
rusticus  exspectat  dum  defluat  amnis:  at  ille 
labitur  et  labetur  in  omne  volubilis  aevum." 


AMERICAN  RED  CROSS  CHILD  WELFARE  WORK 

IN   FRANCE 

By  J.  H.  Mason  Knox,  Jr.,  M.D.,  Baltimore,  Md. 

Lately  Associate  and  Acting  Chief  of  Children's  Bureau,  American  Red  Cross,  France; 
Associate  in  Clinical  Pediatrics,  The  Johns  Hopkins  University. 

I  VENTURE  to  offer  for  this  commemorative  volume  a  brief 
account  of  the  American  Red  Cross  activities  in  behalf  of 
French  children  during  the  latter  part  of  the  war  period.  I  do 
this  with  some  confidence,  because  Sir  William  Osier's  great  interest 
in  all  that  pertains  to  child  life  is  well  known,  and  it  was  my  privilege 
to  hear  this  interest  expressed  when  I  reported  to  him  in  person  at 
Oxford  last  July  on  the  doings  of  the  Children's  Bureau.  Moreover, 
it  is  becoming  increasingly  apparent  that  medical  research  cannot 
be  confined  to  the  laboratory  or  even  to  the  ward,  but  must  extend 
also  to  dealings  with  people  in  social  groups,  to  the  investigation 
of  the  causes  of  their  common  miseries  and  to  the  application  of 
adequate  methods  of  relief.  Progress  in  these  broader  fields  requires 
methods  of  research  not  unlike  those  of  the  clinic. 

France  during  the  latter  months  of  the  war  offered  a  peculiarly 
promising  field  for  child  welfare  work  for  the  following  reasons : 

(i)  The  importance  of  better  work  for  the  children  of  the  nation 
had  been  sounded  throughout  the  land  and  was  recognized  by  all 
intelHgent  citizens. 

(2)  The  birth-rate  of  France,  the  lowest  in  Europe  before  the 
war,  had  sunk  to  less  than  half  its  usual  figure — to  about  8  per  1000 
— a  reduction  which,  if  continued,  would  of  itself  destroy  the  nation. 
It  could  be  claimed,  for  example,  that  in  comparison  to  America, 
every  infant  life  in  France  was  at  least  twice  as  valuable. 

(3)  France  had  already  in  operation  many  activities  tending  to 
reduce  infant  mortahty  and  to  foster  child  life.  Methods  that  have 
been  proven  successful  in  England  and  America  owed  their  origin 
to  France,  notably  the  Consultation  de  Nourissons,  founded  by 
Budin  in  1892,  and  the  Goutte  de  lait  by  Dufour  two  years  later. 

680 


RED  CROSS  CHILD  WELFARE  WORK  68i 

An  older  mutual  benefit  organization  widespread  in  France  is  the 
Mutualite  maternelle,  with  its  many  branches,  which  for  a  small 
sum  of  money  assures  to  all  members  competent  obstetrical  service 
and  an  allocation  permitting  the  mothers  to  rest  for  some  weeks 
after  confinement.  This  society  is  said  to  have  lowered  infant 
mortality  7  per  cent. 

(4)  France  has  enacted  two  laws  which  have  far-reaching  pos- 
sibiHties  in  the  protection  of  early  childhood.  By  the  Loi  Roussel 
every  child  under  two  years  confided  to  a  woman  other  than  its 
mother  for  its  care  becomes  automatically  under  government  super- 
vision. It  insists  that  factories  employing  women  provide  cbambres 
(Tallaitement  for  nursing  mothers  and  crlcbes  for  older  children. 
The  Loi  Strauss,  passed  just  before  the  war,  19 13-14,  allows  an 
allocation  of  one  franc  a  day  for  the  mother,  one  month  before  the 
birth  of  her  child,  and  one  and  a  half  francs  per  day  for  four  weeks 
afterwards  if  she  remains  home  and  cares  for  it. 

Unfortunately  the  exigencies  of  the  great  conflict  interfered 
greatly  with  the  enforcement  of  these  beneficent  regulations. 

In  normal  times  about  five  thousand  women  in  France  are  em- 
ployed in  factories;  during  the  war,  the  number  exceeded  a  million 
— at  once  a  partial  explanation  of  a  low  birth  and  a  high  infant  mor- 
tality rate.  These  facts,  briefly  stated,  indicate  that  the  French  nation 
was  fully  alive  to  the  need  of  conserving  its  children  and  had  led  the 
world  in  devising  methods  to  accomplish  this  end.  With  the  war  and 
the  taxing  of  all  the  resources  of  the  country  for  immediate  measures 
of  defense  many  of  the  activities  on  behalf  of  mothers,  infants,  and 
young  children  had  to  be  curtailed  or  discontinued.  Nearly  all  the 
nurses  and  physicians  under  fifty-five  years  were  called  for  military 
service,  and  many  civilian  hospitals  were  turned  over  to  the  army  or 
closed. 

(5)  America  entered  the  war  in  April,  191 7,  and  in  the  late 
summer  of  that  year  the  Children's  Bureau  was  organized  under 
Dr.  William  Palmer  Lucas  as  part  of  the  Department  of  Civil 
Aff"airs,  American  Red  Cross.  The  other  bureaus  working  in  the 
closest  co-operation  were  the  Bureau  of  Refugees,  the  Tuberculosis 
Bureau,  and  the  Bureau  of  Reconstruction  in  the  War  Zone. 

It  will  be  recalled  that  that  fall  and  winter  and  the  following 
spring  were  very  critical  times  for  the  allied  arms.  The  balance  of 


682  RED  CROSS  CHILD  WELFARE  WORK 

military  power  after  the  defection  of  Russia  seemed  to  favor  Ger- 
many, and  France  was  turning  toward  its  sister  republic  across  the 
sea  to  bring  to  her  the  additional  assistance  needed  to  rescue  her 
from  German  greed. 

It  was  during  these  anxious  months  before  the  fighting  qualities 
of  America's  raw  troops  had  been  tested,  or  the  extent  of  our  mili- 
tary effort  was  fully  appreciated,  that  aid  was  proffered  by  the 
American  Red  Cross  for  the  civilian  population  of  France. 

(6)  The  whole  population,  official  and  unofficial,  wealthy  and 
poor,  without  regard  to  religious  faith  or  social  standing,  accepted 
our  offers  of  assistance  for  the  children  with  the  utmost  gratitude 
and  with  every  evidence  of  cordial  co-operation. 

(7)  Through  the  generosity  of  the  American  people  we  had  large 
means  at  our  disposal,  and  a  constantly  increasing  number  of  care- 
fully selected  physicians,  nurses,  and  others  familiar  with  the  vari- 
ous phases  of  child  welfare  work. 

These,  then,  were  the  outstanding  elements  in  the  unique  situa- 
tion :  (a)  A  great  country  fully  alive  to  the  importance  of  increasing 
and  preserving  its  child  population,  but  with  its  means  of  carrying 
on  its  plans  greatly  curtailed  because  of  a  great  war;  (6)  assistance 
extended  to  all  classes  of  children  in  a  sympathetic,  tactful  manner, 
from  the  large  resources  of  an  allied  sister-republic.  Such  a  com- 
bination of  favorable  circumstances  may  never  occur  again,  and 
they  offered  such  unusual  opportunities  to  demonstrate  certain 
methods  of  infant  welfare  that  it  may  be  worth  while  to  place  them 
on  record. 

The  Children's  Bureau  arrived  in  France  early  in  August,  19 17, 
with  a  staff  of  about  a  dozen  members.  The  number  was  increased 
by  nearly  every  boat  until  100  physicians,  200  nurses,  and  as  many 
more  nurses'  aids  and  other  assistants  especially  interested  in  child 
welfare,  were  in  the  service  of  the  Bureau.  The  effort  from  the  first 
was  not  to  implant  American  methods  upon  the  older  country,  but 
to  assist  it  in  working  out  its  own  problems. 

It  is  not  the  intention  of  this  paper  to  describe  the  work  in  any 
detail,  but  rather  to  mention  briefly  certain  features  of  it  which 
have  general  application  both  at  home  and  abroad. 

Rural  Dispensaries.  One  of  the  first  jobs  the  Bureau  was  asked 
to  undertake  was  the  medical  supervision  of  a  colony  of  500  children 


RED  CROSS  CHILD  WELFARE  WORK  683 

gathered  at  a  large  military  barracks  near  Toul  from  villages  which 
were  subjected  to  gas  attacks.  After  some  months  of  patient  effort 
this  large  group  of  children  was  made  into  a  model  colony.  In  con- 
nection with  it  was  organized  a  dispensary  and  a  hospital,  first  of  a 
few,  later  of  200  beds,  which  ministered  to  the  civil  population  for 
miles  around.  Soon  it  was  learned  that  there  were  large  manu- 
facturing towns  within  reaching  distance  which  were  almost  without 
medical  service.  With  the  support  of  the  American  Fund  for  French 
Wounded  a  dispensary  service  was  established  in  perhaps  a  dozen 
of  these  centers.  Rooms  were  secured  in  each  through  the  kind 
offices  of  the  officials,  and  twice  a  week  at  a  specified  hour,  a  phy- 
sician, nurse,  and  one  or  more  nurses*  aids  would  arrive  by  an  auto- 
ambulance  and  hold  a  clinic.  Simple  supplies  were  carried  in  the 
ambulance,  which  was  used  also  to  bring  urgent  cases  to  the  hospital. 

These  ambulatory  clinics  were  held  at  various  other  sections,  both 
in  France  and  Belgium,  behind  the  fighting  fronts.  The  automobile 
was  always  hailed  with  pleasure.  The  routes  were  known  and  often 
the  doctor  would  be  stopped  and  asked  to  see  some  special  case 
along  the  way. 

The  value  of  this  method  of  bringing  medical  aid  to  a  rural 
population  was  abundantly  proven.  A  similar  system  is  applicable 
in  many  remote  districts  in  other  countries.  Wherever  the  rural 
mail  carriers  go  these  dispensary  units  could  visit,  ministering  to 
the  sick  and  preaching  the  gospel  of  personal  hygiene  and  child 
welfare.  One  automobile  and  staff  could  serve  eight  or  ten  different 
communities.  In  some  towns  a  district  nurse  should  remain  in  resi- 
dence, spending  her  time  in  house-to-house  visiting  and  in  bringing 
patients  to  clinics. 

The  Detection  oj  Contagious  Disease  at  Evian.  The  reception,  care, 
and  distribution  of  the  repatries  at  Evian,  returning  to  France 
after  spending  months  in  the  hands  of  the  enemy,  was  one  of  the 
most  interesting  and  moving  experiences  of  the  war  period.  It  is 
too  well  known  to  require  more  than  a  reference.  To  the  Children's 
Bureau  was  allotted  the  task  of  detecting  and  treating  infectious 
disease  found  among  the  200  to  500  children  passing  through  Evian 
in  two  convoys  each  day.  A  large  hotel  was  converted  into  a  200- 
bed  hospital,  and  with  this  and  a  number  of  detention  wards  and 
convalescent  homes  many  acute  and  chronic  infections  were  stopped 


684  RED  CROSS  CHILD  WELFARE  WORK 

at  the  border  and  prevented  from  spreading  disease  throughout 
France.  Perhaps  no  better  opportunity  has  been  afforded  anywhere 
of  studying  communicable  affections  common  in  childhood. 

In  the  admirable  methods  the  French  introduced  for  bathing, 
delousing,  clothing,  feeding,  and  transporting  these  unfortunate 
elderly  derelicts  and  children  to  their  new  homes  representatives  of 
the  Children's  Bureau  actively  co-operated.  Much  information  was 
obtained  on  the  subject  of  child-placing  in  all  its  phases,  in  hospitals, 
asylums,  colonies,  and  private  homes,  through  our  experience  with 
the  repatrii  children. 

Exhibits  in  Child  Welfare.  Exhibits  as  a  method  of  propaganda 
are  more  familiar  in  America  and  England  than  in  France.  Two 
sorts  of  exhibits  were  arranged  by  the  Children's  Bureau  in  con- 
junction with  the  Rockefeller  Commission  against  Tuberculosis,  in 
which  the  subjects  of  Child  Welfare  and  Tuberculosis  were  graphic- 
ally depicted.  The  larger  exhibits  were  held  in  several  of  the  principal 
cities  of  France,  beginning  at  Lyons.  They  were  opened  with  the 
cordial  approval  and  assistance  of  the  officials  and  prominent  citi- 
zens. The  story  was  told  by  means  of  lectures  by  French  physi- 
cians, by  demonstrations  of  the  exhibits  many  times  each  day,  and 
by  cinema,  indoor  and  outdoor,  to  enormous  crowds,  and  for  the 
first  time  by  a  cleverly  acted  "Punch  and  Judy"  show,  the  guignol, 
which  was  first  introduced  at  Lyons,  and  was  now  used  to  show  to 
delighted  audiences  of  parents  the  bad  results  to  the  baby  of  in- 
diflference  and  neglect,  and  the  happy  consequences  that  follow  its 
proper  care.  In  glass  booths  real  physical  examinations  of  children 
were  conducted;  babies  were  weighed,  bathed,  and  clothed.  The 
value  of  nose  and  throat  work  was  demonstrated  on  the  patients 
and  dental  work  actively  carried  on.  The  attendance  at  Lyons  in 
three  weeks  was  over  170,000,  including  nearly  50,000  school 
children,  and  as  a  result  the  number  of  patients  at  the  welfare  clinics 
in  the  city  were  doubled. 

Other  smaller  exhibits  were  arranged  for  in  several  of  the  de- 
partments of  the  country.  Approximately  two  months  was  spent 
in  a  department — about  a  week  in  each  of  its  larger  cities.  Similar 
lectures  and  demonstrations,  aided  by  lantern  slides  and  cinema, 
told  the  story  of  the  fight  against  tuberculosis  and  the  healthful 
rearing  of  children.  In  each  town  where  interest  was  aroused  active 


RED  CROSS  CHILD  WELFARE  WORK  685 

"follow  up"  work  was  planned  and  started,  if  possible,  through 
existing  organizations.  Thus  the  enthusiasm  stirred  up  by  the 
American  exhibits  was  continued  under  French  auspices. 

Courses  in  Nursing.  It  soon  became  evident  in  our  work  for 
children  that  house  visiting  on  the  part  of  a  tactful  nurse  as  we  know 
her  in  America  was  rarely  done,  and  that  if  our  dispensary  work 
both  in  small  towns  and  large  cities  was  to  be  really  valuable,  it 
should  be  supplemented  by  the  instructive  visits  of  nurses  in  the 
patients*  homes.  Fortunately  many  of  our  American  nurses  had 
been  trained  in  Social  Service,  and  were  able  to  instruct  the  French 
pupil  nurses  in  the  field.  Short  courses  in  health  visiting  were  begun 
in  co-operation  with  the  Rockefeller  Commission  and  independently, 
designed  to  emphasize  the  simple  rules  of  hygiene  as  applied  to  child 
welfare  and  to  tuberculosis,  and  to  lay  especial  stress  on  social  ser- 
vice in  the  home.  Active  assistance  was  given  by  French  physicians, 
who  delivered  the  lectures  and  conducted  the  quizzes  of  the  care- 
fully prepared  course.  Practical  work  for  the  pupil  nurses  was 
obtained  at  the  hospitals  and  dispensaries.  These  courses  were 
given  at  Paris,  Lyons,  Marseilles,  and  elsewhere.  They  attracted 
earnest  women — who,  as  they  completed  their  training,  were  sent  to 
assist  the  trained  nurses  on  the  field. 

Those  who  are  famihar  with  the  great  value  of  home  visiting 
as  a  part  of  the  medical  work  in  America  will  join  in  the  hope  that 
this  little  demonstration  in  France  will  lead  to  its  general  intro- 
duction in  connection  with  every  hospital  and  dispensary. 

Supervised  Play.  We  were  fortunate  in  having  in  the  Bureau  the 
services  of  a  number  of  playground  workers  and  recreational 
experts.  It  was  possible,  therefore,  in  connection  with  all  our 
exhibits  and  in  the  various  colonies  and  institutions  under  our 
charge,  to  give  practical  instruction  and  demonstrations  of  the 
value  of  supervised  play  in  physical,  mental,  and  moral  training. 
In  the  games  such  qualities  as  initiative,  self-reliance,  pluck,  team- 
play,  and  so  forth,  were  stressed.  The  children  quickly  learned  the 
games,  and  it  is  expected  that  many  French  children  who  loved  to 
romp  when  shown  how  and  to  whom  this  kind  of  play  was  novel 
will  not  forget  it  when  the  Americans  have  gone  home. 

Intensive  Infant  Welfare  Work.  What  would  happen  if  every 
baby  in  a  limited  community  received  proper  care?  We  had  unusual 


686  RED  CROSS  CHILD  WELFARE  WORK 

opportunity  to  begin  the  answer  to  this  question  in  a  number 
of  places  because  of  the  co-operation  of  French  officials,  who 
placed  at  our  disposal  the  accurate  statistical  information  of  the 
district.  A  ward  in  Paris  and  several  other  limited  areas  in  town 
and  country  were  selected.  Each  day  the  names  and  addresses  of 
the  babies  born  in  these  areas  were  sent  to  the  Red  Cross  repre- 
sentatives. These  infants  were  immediately  visited  and,  with  the 
aid  of  French  agencies,  adequately  helped  if  there  was  need.  That 
is,  it  was  made  financially  possible  for  the  mother  to  remain  home 
and  nurse  and  care  for  her  baby,  and  she  was  encouraged  to  so  do. 
She  received  instruction  both  at  her  home  and  at  a  nearby  welfare 
station.  Each  case  was  studied  individually,  and  the  treatment 
required  to  "save  the  baby"  by  its  own  mother,  administered. 
Thus  each  dependent  baby  in  the  district  was  given  more  of  an 
equal  chance  with  the  baby  of  the  well  to  do. 

A  society  was  organized  in  the  14th  Arrondissement,  Paris, 
under  the  patronage  of  Maire  Ferdinand  Brunot,  "Patronage 
Franco- American  de  la  premiere  Enfance,"  to  begin  this  intensive 
work  there.  Through  this  means  it  was  hoped  greatly  to  reduce 
infant  mortality  in  that  crowded  district  and  to  demonstrate  that 
babies  can  be  saved  if  those  care  sufficiently  who  know  and  have. 
We  are  confident  that  this  "100  per  cent  work"  for  which  this 
Patronage  Society  stands  is  a  distinct  forward  step  in  Infant  Wel- 
fare Work,  and  that  time  will  demonstrate  that  the  plan  is  practical 
and  that  this  method  born  in  Paris  as  a  war  measure  may  prove 
a  model  applicable  in  other  times  and  places. 

Co-ordination  of  Child  Welfare  Work.  With  the  well-known 
imagination  and  impulsiveness  of  the  French  people  and  their 
fondness  for  children  it  is  not  difficult  to  understand  that  there 
are  in  France  many  kinds  of  organizations  and  societies  devoted  to 
child  care.  Not  a  small  part  of  the  labor  of  the  Bureau  was  to  help 
the  most  deserving  and  to  co-ordinate  the  activities  of  those  deal- 
ing with  similar  problems. 

Many  grants  made  by  the  Red  Cross  to  children's  societies  and 
institutions  reduced  in  their  resources  because  of  the  war  were 
conditional  upon  the  introduction  of  some  suggested  improvement 
in  plant  or  method.  It  seemed  in  many  instances  that  this  merging 
of  interests  could  be  secured  only  through  American  suggestion, 


RED  CROSS  CHILD  WELFARE  WORK  687 

but  when  once  brought  about  will  be  continued  in  the  future.  In 
Marseilles  and  Lyons,  for  example,  practically  all  the  children's 
organizations  were  brought  for  the  first  time  into  cordial  affiliation. 
Such  were  a  few  of  the  more  instructive  attempts  made  by  the 
American  Red  Cross  to  come  to  the  aid  of  French  children  in  the 
hour  of  their  need.  The  occasion  was  unusual.  In  the  process  France 
became  in  a  sense  a  voluntary  laboratory  for  the  testing  of  many 
phases  of  child  care.  It  was  possible,  therefore,  not  only  to  bring 
assistance  to  the  present  generation  of  children  of  this  gifted  and 
industrious  nation,  but  perhaps  also  to  indicate  some  methods  by 
which  child  life  may  become  more  healthful  and  happy  in  other 
countries  as  well. 


MILITARY  MORALE 
By  Edward  L.  Munson, 

Brigadier  General,  General  StaflF;  Colonel,  Medical  Corps,  U.  S.  A. 

WHILE  the  above  subject  is  one  not  directly  related  to  the 
practice  of  medicine,  it  still  is  not  wholly  dissociated 
therefrom,  as  it  not  infrequently  pertains  to  group  states 
of  mind  quite  as  abnormal  and  irrational  as  those  which,  in  the 
individual,  come  to  the  attention  of  the  alienist.  Further,  it  may 
have  a  certain  medical  interest  from  the  fact  that,  so  far  as  the 
United  States  were  concerned,  the  proposal  for  the  institution  of 
morale  work,  its  successful  experimental  application,  and  its  or- 
ganization as  a  military  agency,  were  all  carried  out  by  a  member 
of  the  Medical  Department. 

One  of  the  many  blunders  made  by  Germany  during  the  war  in 
its  psychological  estimate  of  other  peoples  was  in  deciding  that  the 
United  States  could  not  put  forward  a  disciplined  army  of  a  fighting 
quality  equal  to  the  best  that  the  Central  Powers  were  able  to 
present.  To-day  this  mistake  is  conceded  in  Berlin,  for  it  was 
American  aggressiveness,  quite  as  much  as  actual  or  potential  force, 
that  broke  the  heart  of  German  resistance  and  showed  the  enemy 
not  only  that  he  could  not  win,  but  that  stalemate  tactics  would 
not  be  tolerated  and  that  he  was  sure  to  lose. 

The  morale  of  the  American  soldier  was  perhaps  one  of  the  most 
impressive  things  pertaining  to  his  part  in  the  war.  The  triple  chain 
of  confidence,  cheerfulness,  and  willingness  to  suffer  any  sacrifice, 
so  bound  the  troops  together  as  to  make  them  unbeatable.  They 
knew  it  all  the  time — it  did  not  take  long  for  the  Germans  to  find  it 
out.  The  latter  had  spent  generations  in  developing  their  armies  to 
such  a  degree  of  efficiency  that  their  organization  was  proclaimed 
to  be  the  best  ever  upbuilt.  Probably  so  it  was,  from  the  mechanical 
aspect;  but  it  lacked  in  animating  spirit  to  have  full  fighting  strength. 
From  their  first  contact  with  American  troops,   from  Chateau 

688 


MILITARY  MORALE  689 

Thierry  to  Sedan,  the  flower  of  militaristic  Germany  was  swept 
back,  foot  by  foot,  yard  by  yard,  and  mile  by  mile,  until  only  the 
armistice  saved  retreat  from  becoming  rout.  These  things  were  done 
by  men  who,  called  from  the  farm  and  bench,  became  in  a  few 
months  an  army  of  courageous,  confident,  self-sacrificing  soldiers, 
whose  presence  the  enemy  feared  and  detested. 

The  sudden  and  stupendous  expansion  of  an  army  to  represent 
the  might  of  an  unprepared  nation  caused  the  full  force  of  the  War 
Department  to  concentrate  at  first  on  the  problems  of  mobilization, 
organization,  and  procurement  of  material.  With  these  preparations 
the  spirit  of  patriotism  was  quickened. 

It  was  felt,  however,  that  morale,  which  with  training  is  the 
basis  of  discipline,  was  so  fundamentally  important  a  matter  that 
its  growth  should  not  be  matter  of  chance.  Napoleon  had  said,  "In 
war,  the  moral  is  to  the  physical  as  three  is  to  one,"  and  all  writers 
had  recognized  that  good  morale  was  prerequisite  to  military  suc- 
cess. But  the  question  of  how  to  influence  morale  directly  was 
largely  unattacked. 

In  January,  19 17,  the  writer,  in  an  editorial  entitled  "The 
Soul  of  an  Army,"  said:  "There  must  be  systematized  education 
and  training  in  the  psychology  of  the  soldier  and  of  the  war.  This 
field  is  not  now  covered.  It  is  a  *No  Man's  Land*  into  which  neither 
line  nor  staff"  penetrate."  Again  on  March  2,  1918,  in  a  memorandum 
entitled,  "Need  for  the  Systematized  Psychological  Stimulation  of 
Troops  in  the  Promotion  of  Fighting  Efficiency,"  he  further  urged 
the  importance  of  the  matter  on  the  General  Staff",  with  a  result  that 
a  series  of  conferences  was  held  on  the  subject  by  representatives  of 
various  organizations  having  to  do  with  the  prosecution  of  the  war. 
In  the  meantime,  the  writer  had  been  transferred  to  Camp  Green- 
leaf,  Georgia,  and  as  Commanding  Officer  there  tried  out  in  actual 
field  work,  on  a  camp  of  some  35,000  men,  the  ideas  advanced  in 
theory.  As  a  result  of  these  conferences,  and  the  successful  demon- 
stration of  the  practical  value  of  the  work  at  Camp  Greenleaf,  the 
General  Staff"  decided  to  authorize  the  work  and  place  it  on  a  sound 
basis  throughout  the  Army. 

Accordingly,  the  following  order  was  issued  by  the  War  De- 
partment: 


690  MILITARY  MORALE 

*'i.  There  is  hereby  created  a  Morale  Branch  within  the  General 
Staff.  ... 

"2.  The  general  functions  of  the  Morale  Branch  relate  to  the  improve- 
ment of  the  efficiency  of  the  soldier  through  the  betterment  of  morale. 

"3.  The  Morale  Branch  shall  have  cognizance  and  control  of  the  fol- 
lowing: 

"(a)  The  initiation  and  administration  of  plans  and  measures  to 
stimulate  and  maintain  the  morale  of  troops. 

"(6)  The  organization,  training,  co-ordination  and  direction  of  all 
agencies,  military  and  civil,  operating  within  military  zones,  in  so  far  as 
they  serve  to  stimulate  and  maintain  morale  in  the  army. 

"(c)  Co-operation  with  any  morale  agencies  of  the  General  Staffs 
of  Allied  countries  in  connection  with  military  morale. 

"(</)  The  supervision,  co-ordination  and  direction  of  activities  in  the 
various  departments,  corps,  and  bureaus  of  the  army  for  stimulating 
morale  within  organizations  or  among  producers  of  munitions. 

"(e)  The  supervision,  co-ordination  and  utilization,  so  far  as  may 
properly  be  accomplished  by  military  authority,  of  all  recognized  civilian 
agencies  which  might  contribute,  directly  or  indirectly,  to  the  enhancement 
of  morale.  To  this  end,  close  relations  will  be  established,  through  the  Third 
Assistant  Secretary  of  War  as  Director  of  Civilian  Relations,  by  the  Morale 
Branch,  with  all  officially  recognized  agencies  for  the  improvement  of 
morale  in  the  Army  or  Nation.  It  will  not  give  official  recognition  to  un- 
recognized voluntary  agencies,  though  treating  them  with  respect  and 
consideration." 

The  writer  was  made  Chief  of  the  new  Branch,  which.with  its 
military  organization,  including  a  number  of  various  experts,  as 
psychologists,  sociologists,  newspaper  men,  artists  and  cartoonists, 
advertising  men,  linguists,  and  others,  at  once  set  about  the  system- 
atic stimulation  of  military  morale. 

It  is  not  practicable  at  this  time  to  go  into  details  as  to  how  this 
was  accomplished,  and  is  being  accomplished;  for  the  task  is  still 
uncompleted,  and  it  is  obvious  that  work  of  this  sort  is  best  accom- 
plished as  unobtrusively  as  possible.  Disclosure  of  methods  and 
purposes  would  arouse  unconscious  resistance  and  render  far  less 
plastic  the  human  material  which  must  be  handled.  Suffice  it  to 
say  that  exact  methods  were  worked  out  in  relation  to  the  psy- 
chological forces  which  render  them  as  relatively  controllable  and 
intelligently  directed  as  the  similarly  unseen  forces  of  electricity  or 


MILITARY  MORALE  €91 

radium,  and  which  will  later  be  given  out  when  such  may  be  done 
without  detriment  to  military  purposes.  An  organization,  sensitive 
down  to  the  private  in  the  company,  was  created  whereby  the 
morale  agencies  could  function  to  the  lowest  unit.  By  it,  favorable 
states  of  mind  were  induced  and  undesirable  acts  averted  by  pro- 
cesses more  or  less  analogous  to  the  elimination  of  infectious  disease 
and  the  prevention  of  epidemics. 

Morale  work  has  its  purposes  quite  as  much  in  peace  as  in  war. 
In  the  latter,  patriotic  purpose,  mutual  protection,  and  other  factors 
tend  to  hold  men  together.  But  the  signing  of  the  armistice,  and 
relief  from  the  military  tension  along  the  above  Hnes,  released  a 
horde  of  pent-up  emotions  which  created  most  difficult  adminis- 
trative problems.  These  states  of  mind  it  was  the  duty  of  the  Morale 
Branch  to  handle.  Perhaps  it  may  claim  a  certain  efficiency  in  this 
respect,  since  nearly  two  million  men  have,  at  this  writing,  been 
demobilized  and  returned  to  civil  life  without  the  slightest  disorder, 
where  riots  and  disturbances  against  authority  have  repeatedly 
occurred  in  the  troops  of  other  nations  during  the  same  period. 
Also  the  men  have  been  absorbed  back  into  civil  life  in  a  good  frame 
of  mind  toward  the  Government  and  Army,  untainted  by  political 
heresies. 

There  are  many  qualities  expressive  of  military  morale.  Some 
pertain  to  fighting  only — others  are  stepping  stones  to  that  end. 
Discipline  imphes  both  training  and  morale.  Training  gives  ability 
to  fight,  while  morale  is  desire  to  fight.  Both  are  necessary  to  victory. 
Morale  is  to  an  army  what  temper  is  to  the  Damascus  blade,  a 
"fighting  edge"  with  a  resihency  no  shock  can  crack.  If  morale  is  as 
important  as  this,  it  is  important  enough  to  make  every  effort  to 
cultivate  it,  and  it  thrives  under  such  culture. 

But  morale  is  not  merely  enthusiasm  or  mental  courage  or  the 
fighting  spirit.  It  is  all  these,  and  more.  It  has  a  sterner  element.  It 
is  that  mental  hardening  which,  in  a  body  of  troops,  continues  to 
function  after  everything  else  has  broken.  It  is  a  quality  which  at 
the  last  desperate  moment  continues  to  function  after  all  the  condi- 
tions which  have  created  it  have  disappeared.  It  is  not  only  the  will 
to  win,  but  the  refusal  to  consider  anything  else  as  possible.  Military 
morale  accordingly  is  mental  fitness  of  troops  for  the  work  of  war. 
It  is  to  the  mind  what  "condition"  is  to  the  body;  good  morale  is 


692  MILITARY  MORALE 

good  mental  "condition,"  bad  morale  is  bad  mental  condition. 
The  state  of  good  morale  must  be  relatively  lasting,  for  the  test  of 
good  morale  is  time  and  adversity. 

In  an  army  of  a  democratic  government  the  soldier  fights  well 
only  for  ideals.  Money  or  material  reward  is  no  inducement  to  the 
American  soldier  to  face  the  bullets  of  the  Argonne,  but  he  seeks 
out  death,  with  a  smile  on  his  lips,  as  the  champion  of  ideals.  He 
must  know  the  reasons  and  principles  of  the  cause  for  which  he 
fights;  and  besides  knowing,  he  must  believe  in  them. 

The  morale  of  the  army  of  democracy,  therefore,  must  rest 
solidly  upon  the  basis  of  conviction.  If  the  soldier  does  not  possess 
this  on  entering  the  army — and  all  do  not — it  must  be  given  to  him. 
Ideals  are  an  essential  part  of  his  equipment.  It  follows,  therefore, 
that  information  and  education,  the  mainstay  of  democracy  in 
peace,  must  be  its  strength  in  war. 

There  is  such  a  thing  as  morale  based  on  sordid  motives,  but  its 
nature  is  comparatively  temporary,  and  its  quality  is  inferior. 
Such  was  the  German  morale,  founded  on  a  desire  and  expectation 
to  take  p>ossession  by  force  of  the  material  things  of  this  world.  It 
was  the  same  morale  that  held  together  the  buccaneers  and  free- 
booters of  all  ages.  But  it  could  be  successful  only  in  material 
success.  Hence  the  extraordinary  spectacle  of  the  powerful  German 
armies,  everywhere  fighting  in  enemy  territory  and  successful  ac- 
cording to  the  map,  falling  apart  without  cohesiveness  when  defini- 
tively balked  of  their  prey  and  finding  their  booty  of  the  past  snatched 
from  them.  They  had  no  other  ideals  than  those  of  materialism  to 
sustain  and  inspire  them.  When  these  failed,  morale  was  lost. 

To  these,  the  Allies  opposed  the  imponderables.  Their  ideals 
of  right,  truth,  honor,  justice,  and  liberty  shone  more  brightly  after 
four  years  of  adversity  and  became  more  precious  as  they  were 
threatened.  The  thin  Allied  line  might  give  ground  under  the  mighty 
blows  of  the  war  engine;  it  might  bend  and  stretch,  but  it  never 
broke,  because  of  the  flaming  spirit  of  the  ideal  that  made  death 
better  than  submission. 

The  Germans  bolstered  up  their  men  with  falsehood,  as  by  the 
same  way  they  sought  to  undermine  the  fighting  spirit  of  their  foes. 
They  could  be  successful  only  so  long  as  their  deceit  and  falsehood 
were  not  found  out.  When  this  happened,  they  lost  confidence  in 


MILITARY  MORALE  693 

their  cause,  their  leaders,  and  themselves.  America,  through  its 
morale  methods,  fights  lies  with  truth.  Its  cause  is  just.  It  knows 
that  against  an  unholy  cause  "the  truth  is  mighty  and  will  prevail." 
It  knows  that  what  it  does  in  making  a  better  soldier  will  make  him 
later  a  better  citizen.  Its  ideals  are  such  as  stimulate  its  men  to 
victory  and  confound  its  foes.  And  right  ideals  win.  Even  such  a 
crass  materialist  as  Bismarck  said,  '*  It  is  the  imjx)nderables  which 
weigh  the  most." 


PHASES  OF  WAR  SURGERY.  EXTENSIVE,  HIGHLY 
DISFIGURING  WOUNDS  OF  THE  FACE 

By  Charles  A.  Powers,  M.D.,  Denver,  Colo. 

Professor  Emeritus  of  Surgery  in  the  University  of  Colorado. 
Formerly  Major,  M.  C,  U.  S.  Army 

THE  incidence  of  high-explosive  casualties  in  the  present  war 
has  occasioned  wounds  hitherto  unknown.  Of  these,  the 
severely  disfiguring  injuries  of  the  face  are  of  marked  im- 
portance. The  carrying  away  of  the  lower  part  of  the  face  may 
be  immediately  fatal  (hemorrhage,  shock,  closure  of  the  glottis), 
or  fatality  may  result  later  through  sepsis,  secondary  hemorrhage, 
pneumonia.  In  a  given  percentage  of  cases,  however,  the  wounded 
soldier  survives,  only  too  often  to  be  repulsive  through  his  disfigure- 
ment, the  reduction  of  which  to  the  greatest  possible  degree  has 
furnished  the  surgeon  with  difficult  and  perplexing  problems, 
problems  enlisting  his  sympathy  as  well  as  his  skill.  Not  only  should 
the  soldier  be  made  to  present  as  comely  an  appearance  as  possible, 
but  he  should  be  able  (wounds  of  the  lower  part  of  the  face)  to 
masticate  well  and  to  speak  intelligibly.  In  gaining  the  best  results, 
the  surgeon  must  have  the  intelligent  co-operation  of  the  dentist; 
fragments  of  bone  must  be  appropriately  held  by  splints,  dentures 
must  be  carefully  made  and  applied.  This  co-operation  between 
surgeon  and  dentist  has  found  in  this  war  application  previously 
unknown. 

The  subjoined  history  and  photographs  are  presented  without 
further  comment. 

Case.  P.  C,  aged  forty-one  years,  single.  Regt.  Adjutant  3°"  Mixt. 
Zouaves.  Serial  No.  4441.  Wounded  by  fragments  of  shell  while  in  action 
May  18,  19 1 6.  Admitted  to  the  American  Ambulance  Hospital  of  Paris, 
Ward  178,  May  30,  19 16. 

Examination.  Compound,  comminuted  fractures  of  the  anterior, 
lower  portions  of  both  superior  maxillae,  of  both  palate  bones,  of  the 
vomer  and  of  the  anterior  portion  of  the  inferior  maxilla.  Much  loss  of 

694 


Fig.    I.     Condition  on  Admission,   May 
30,  1916. 


Fig.    2.      Approximation    of    Upper    I.ip 
AND  Chin,  June  6,  IQ16. 


Fig.  3.     July  10,  1916,  Upper  Lip 
Formed. 


Fig.  4.    August  29,    19 16,  Formation  of 
Lower  Lip  and  Mouth. 


Fig.  5.     September  2,  1916. 


Fig.  6.     April  ii,  1917. 


Fig.   7.     Condition   on  Discharge,  May 
2.  I9I7- 


PHASES  OF  WAR  SURGERY  695 

bone  substance,  loss  of  all  teeth  excepting  some  upper  and  lower  molars. 
Severe  laceration  and  much  loss  of  substance  (considerable  loss  of  mucous 
membrane)  of  the  soft  tissues  of  the  face,  especially  those  of  upper  lip, 
lower  lip,  and  chin.  Severe  lacerations,  with  considerable  loss  of  substance, 
of  the  tongue.  All  wounds  septic  and  foul.  Moderate  fever.  (Facial  condition 
on  admission  shown  in  Fig.  i.) 

Treatment.  Hourly  irrigations  with  permanganate  solution,  1-8000, 
suitable  tube  feeding,  attention  to  bowels,  removal  of  eclats  d'obus  (local 
anesthesia),  from  front  of  neck;  sitting  posture.  (The  patient,  a  very 
intelligent  professional  soldier,  co-operates  with  the  surgeon  and  nurses 
in  every  way.) 

Three  days  after  admission,  June  2,  19 16,  under  local  anesthesia,  the 
fragments  of  the  upper  lip  and  those  of  the  soft  tissues  of  the  chin  were 
loosely  brought  together  by  sutures  of  silk- worm  gut  and  horsehair.  (Fig.  2, 
picture  taken  June  6,  19 16.)  (Note.  June  10  the  patient  is  up  and  about, 
doing  well.  Slight  suppurative  fever.) 

July  3,  19 1 6.  The  upper  lip  drops  (Note:  I  am  of  the  thought  that  an 
attempt  should  have  been  made  to  elevate  this  at  the  time  of  the  opera- 
tion of  June  2,  despite  the  severely  septic  condition  of  the  wound. — 
C.  A.  P.),  and  under  local  anesthesia  both  sides  of  the  upper  lip  and  the 
adjacent  portions  of  the  wound  are  dissected  free,  lifted,  and  held  up  by 
large,  stay,  suture-guys,  these  suture-guys  running  to  the  soft  parts  over 
the  anterior  portions  of  the  malar  bones.  (Guy  scars  shown  in  Fig.  3.) 
In  addition,  the  right  side  of  the  lower  lip  is  dissected  loose  from  the 
tissues  to  which  it  had  become  adherent  and  brought  up  toward  the  upper 
lip,  being  held  in  place  by  sutures.  Tissues  of  chin  loosened  and  approx- 
imated as  far  as  possible. 

Note:  July  7.  Left  side  of  lower  lip  loosened  and  held  up  by  stay- 
sutures. 

July  10.  These  latter  procedures  have  been  successful.  (Fig.  3,  photo- 
graph taken  this  day.)  Note,  July  20:  The  opening  in  the  face  is  contracting 
rapidly. 

July  31.  Ether.  Further  plastic  approximation  of  tissues.  Necrosed 
bone  removed  from  right  side  of  inferior  maxilla.  (Small,  loose  fragments 
have  been  taken  from  all  fractured  bones  from  time  to  time.) 

August  19,  1916.  Operation,  ether.  Complete  freeing  of  all  tissues 
of  the  face,  extensive  freeing  of  tissues  of  chin  well  down  on  neck.  Section 
of  the  cheek  on  right  side  at  angle  of  present  mouth.  Mucous  membrane 
brought  to  skin.  Preliminary  attempt  at  formation  of  lower  lip.  Chin  tissues 
brought  up  and  fastened  to  lower  lip. 

August  26.  Further  plastic  operation.  Right  cheek  slit  out  about  i^ 


696  PHASES  OF  WAR  SURGERY 

inches.  Mucous-skin  approximation.  Right  angle  of  mouth  formed.  Left 
cheek  slit  out  about  f  inch.  Remains  of  lower  lip  brought  over  from  right 
side  and  fastened  to  tissues  of  left  side,  thus  forming  a  lower  lip.  Chin 
tissues  undermined  and  brought  up.  (Fig.  4,  taken  August  29,  1916,  shows 
formation  of  mouth  and  lower  lip.) 

Fig.  5,  September  2,  1916,  shows  the  result  of  this  procedure;  at  this 
time  (September  2d)  the  patient  has  not  yet  complete  control  of  the  saliva. 

Small,  additional  plastic  operations  were  done  on  September  17th, 
October  9,  and  October  31. 

The  patient  spent  the  winter  of  191 6-1 7  in  an  annex  hospital  at  Clichy 
awaiting  further  plastic  procedures. 

April  16,  191 7.  Ordinary  Nelaton  operation  for  the  relief  of  the  hare-lip 
shown  in  Fig.  5  (September  2,  1916)  and  Fig.  6  (April  1 1,  1917).  In  this  last 
picture  the  smoothing  out  of  the  depressed  scars  and  the  return  of  a 
molded  facial  contour  may  be  noted.  At  this  time  the  patient  is  able  to 
control  the  flow  of  saliva. 

May  10,  19 1 7.  The  hare-lip  has  been  satisfactorily  corrected  (Fig.  7). 
The  patient  retains  saliva  well.  There  is  firm,  bony  union  in  the  fractured 
mandible.  The  dental  department  (Dr.  Darcissac)  has  provided  the  patient 
with  cleverly  made,  practically  useful  and  excellent  appearing  artificial 
teeth.  He  controls  saliva  perfectly.  Small  operations  have  freed  an  adherent 
tongue.  He  speaks  and  eats  well  and  presents  the  quite  comely  appearance 
shown  in  Fig.  7.  (Photograph  May  2,  191 7.)  His  general  health  has  been 
excellent  since  a  month  after  his  injury. 

May  25,  191 7.  Patient  discharged. 

July  4,  19 1 7.  The  patient  writes  me  (C.  A.  P.)  of  a  recently  and  happily 
contracted  marriage. 

Continued  observation  of  a  fairly  large  series  of  somewhat  sim- 
ilar cases  serves  to  impress  upon  me  the  advantage  of  complete 
military  control  of  the  given  patient  (fortunately  these  cases  are 
exceedingly  rare  outside  of  the  casualties  of  battle),  the  importance 
of  deliberate  and  careful  daily  inspection,  as  well  as  the  retention 
of  the  patient  in  a  single  hospital  and  continued  attention  by  a 
single  surgeon.  Continuity  of  service,  not  often  possible  in  war 
surgery,  makes  for  the  best  results.  It  seems  trite  to  say  that  the 
earlier  skilled  attention  is  afforded  these  distressing  cases,  the  better 
will  be  the  results. 


A  PSYCHOTIC  EPISODE  IN  ROMAN  HISTORY 
a  study  of  the  abnormal  psychology  of  nations 

By  Charles  L.  Dana 

I  AM  calling  attention  to  a  short  period  of  human  history  between 
50  B.  c.  and  44  B.  c,  during  which  time  there  was  an  extraordi- 
nary upset  in  human  affairs — the  world  changed  hands. 

I  wish  to  show  that  the  phenomena  of  that  period,  as  ex- 
hibited by  certain  national  events,  resemble  a  psychotic  episode 
in  the  human  individual.  The  analogy  is  not  altogether  fanciful, 
and  is  perhaps  of  more  than  academic  interest;  for  it  seems  to  me 
that  it  is  suggestive  of  a  new  line  of  study — that  of  the  abnormal 
psychology  of  races  considered  as  units.  The  study  is  a  difficult  one, 
and  what  I  present  may  be  nothing  more  than  suggestive,  but  I 
feel  satisfied  that  it  is  worth  while,  for  such  studies  may  help  us  in 
interpreting  and  forecasting  national  events  and  progress. 

In  studying  the  career  of  an  individual  for  psychological  pur- 
poses, we  try  to  learn  the  make-up  of  his  character,  to  get  at  his 
personahty,  to  find  out  the  amount  and  quality  and  proportions  of 
his  mental  endowments.  Some  persons  are  simply  defective  quanti- 
tatively— they  lack  the  mind  stuff,  they  are  imbecile  or  childish  in 
intelligence;  others  are  lacking  in  some  single  form  of  endowment, 
such  as  emotion,  self-control,  power  of  decision,  or  of  initiative, 
being  otherwise  perhaps  brilliantly  intelligent.  These  are  said  to 
have  a  constitutional  psychopathic  inferiority.  Others  have  an  abnor- 
mal make-up,  with  overdevelopment  of  anti-social  instincts ;  they  form 
the  criminals,  the  perverts,  the  eccentric  and  abnormal  types.  They 
are  said  to  have  a  psychopathic  personality. 

In  the  life  history  of  a  normal  individual,  the  ordinary  methodical 
working  of  his  thoughts,  emotions,  or  behavior  may  become  seriously 
disordered.  Then  we  say  he  has  a  psychosis  or  mental  sickness.  This 
morbid  mental  condition  may  be  slight  and  episodal,  or  it  may  be 

697 


698      A  PSYCHOTIC  EPISODE  IN  ROMAN  HISTORY 

persistent  and  lead  to  the  loss  of  his  health,  property,  personal 
responsibility,  and  death. 

The  history  of  a  race  or  nation  may  be  studied,  just  as  we  study 
the  career  of  an  individual.  We  may  study  its  behavior  for  the  pur- 
pose of  determining  its  normality,  or  to  find  whether  there  is  anything 
in  the  racial  make-up  that  is  comparable  to  a  psychosis,  or  an 
inferiority,  or  psychopathic  personality,  or  a  quantitative  mental 
defect.  This  is  in  line  with  the  present  trend,  viz.,  that  of  studying 
behavior  as  well  as  that  of  applying  the  results  of  introspection,  for 
the  purpose  of  determining  the  condition  of  the  mind. 

As  we  consider  the  history  of  nations,  I  think  we  can  recall  in- 
stances in  which  there  have  occurred  some  things  characteristic  of 
the  psychoses. 

It  is  easy,  for  example,  to  conceive  of  a  national  exhaustion 
psychosis.  This  would  be  characterized  by  a  general  clouding  and 
confusion,  by  indecision,  by  hallucination,  lack  of  insight  or  fore- 
sight, and  a  general  collapse  of  capacity  to  care  for  the  person  or  its 
possessions.  We  may  be  seeing  such  things  at  the  present  time. 
There  was  certainly  a  psychotic  confusion  in  Germany  after  thebreak- 
up  of  Charlemagne's  empire  in  the  ninth  century.  After  three  or  four 
hundred  years  of  futile  wrangling  and  fighting,  the  only  result  was 
the  establishment  of  276  feeble  indep>endent  states. 

There  are  races  which  may,  through  partial  deterioration,  show 
a  constitutional  psychic  inferiority — like  the  present  race  of  the 
Persians,  and  that  of  certain  Nyro  republics.  Perhaps  the  history 
of  Korea  illustrates  this  also. 

Some  nations  seem  to  have  what  is  equivalent  to  a  psychopathic 
personality,  i.e.,  they  are  abnormal  in  certain  lines  of  their  develop- 
mental activities.  This  was  perhaps  true  of  the  Phoenicians,  whose 
civilization  was  characterized  by  ambition  to  gain  money,  and  who 
contributed  nothing  to  the  progress  of  the  world  in  the  domain  of 
science,  art,  letters,  or  of  mechanical  or  agricultural  invention  dur- 
ing the  whole  of  their  history. 

A  quality  of  constitutional  inferiority  may  be  said  to  characterize 
the  Turks — "a  race,"  says  John  Fiske,  "politically  unteachable  and 
intellectually  incurious,  which  has  contributed  absolutely  nothing 
to  the  common  weal  of  mankind." 

There  are  races  which  belong  to  the  high  grades  of  feeble-minded- 


A  PSYCHOTIC  EPISODE  IN  ROMAN  HISTORY      699 

ness.  These  races  may  show  some  intelligence,  but  they  have  not 
enough  to  enable  them  to  exist  nationally,  except  as  dependents. 
A  primitive  and  undeveloped  race,  however,  may  not  be  a  feeble- 
minded one,  for  the  test  of  intelligence  lies  in  the  power  of  living 
with  some  degree  of  order  and  happiness  through  its  own  exertions, 
like  the  North  American  Indians  and  Esquimaux. 

The  emotional  state  is  the  most  unstable  of  the  elements  of 
mental  life,  the  most  easily  affected  by  the  strains  and  tragedies 
of  life,  and  the  most  easily  communicated  to  masses.  All  nations  are 
more  or  less  subject  to  emotional  outbursts,  to  contagious  obsessions, 
to  illusions  or  misinterpretations  of  data.  When  these  things  pass 
beyond  what  the  average  intelligence  and  education  of  the  people 
should  correct,  they  come  within  the  group  of  morbid  mental  states. 
The  emotional  attitude  of  the  Greeks  was  characterized  by  obsessive 
passion  for  local  and  personal  liberty,  not  for  a  large  community 
welfare.  This  led  to  their  undoing.  The  French  had  in  1870  an  attack 
of  episodal  pithiatism,  developed  out  of  the  exhaustion  and  suffering 
of  previous  years.  They  are  said  now  by  a  German  writer  to  have  a 
"Galhc  psychopathy"  characterized  by  a  passion  for  revenge  I 

It  is  too  soon  to  characterize  the  development  and  spread  of 
Bolshevism,  but  it  is  some  form  of  racial  or  national  psychosis;  a 
great  national  movement  based  on  the  results  of  deprivation  and 
suffering  and  stimulated  by  delusions — as  we  believe — or  by  mis- 
interpretations of  the  laws  of  sound  national  development. 

Thus  I  am  sure  it  is  safe  to  say  that  races,  whether  living  under 
the  common  arrangements  of  organized  government  or  not,  are 
quite  proper  objects  of  studies  in  abnormal  psychology.  Such  study 
may  help  to  explain  the  rise  and  fall  of  nations  and  civiHzations. 

Historians  have  in  the  past  attempted  to  describe  the  cause  of 
the  decHne  of  individual  races  and  civiHzations,  but  their  explana- 
tions have  generally  been  based  upon  certain  incidental  conditions, 
such  as  an  excessive  amount  of  war,  the  conditions  of  the  soil,  dev- 
astations made  by  famine,  epidemics,  etc.  These  conditions  all  did 
exist,  but  they  persisted  in  a  measure  because  of  the  defects  in  the 
organization  and  mental  quahties  of  the  race.  One-sixth  of  Italy 
s  uninhabitable  on  account  of  malarial  conditions,  yet  these  could 
be  removed  if  the  people  and  its  government  wished,  i.  e.,  if  it 
had  the  mentality  to  initiate  reform. 


700     A  PSYCHOTIC  EPISODE  IN  ROMAN  HISTORY 

Mr.  Flinders  Petrie,  in  his  "Revolutions  of  Civilization,"  has  con- 
tended that  civilization  is  an  intermittent  phenomenon,  that  the  civil- 
ization of  certain  dynasties  of  Egypt  went  through  periods  of  develop- 
ment and  decHne,  and  that  the  same  process  took  place  in  Europe. 
He  puts  the  civiHzation  which  began  in  the  fifth  century  B.C.,  and  ended 
in  the  Age  of  Constantine,  as  a  seventh  period  of  European  evolution. 

Professor  Petrie  does  not  attempt  to  explain  these  recurrent 
phenomena,  however,  nor  has  anyone,  so  far  as  I  know,  attempted 
it  in  any  general  way.  The  suggestion  that  it  may  be  due  to  the 
faulty  make-up  in  the  mentality  of  races  is  at  least  worth  consider- 
ing. We  know  that,  given  a  certain  personality,  if  it  is  subject  to 
depressing  or  irritant  conditions,  it  develops  a  special  psychosis 
corresp>onding  to  the  mechanism  of  the  individual's  character.  So, 
when  a  nation  or  race  is  made  up  on  a  certain  pattern,  it  will  react 
to  exhausting  or  depressing  stimuli,  in  accordance  with  its  mental 
mechanisms. 

Let  us  now  see  what  was  the  "make-up"  of  the  Roman  race. 

The  members  of  this  race  were  certainly  not  constitutionally 
inferior  or  psychopathic.  They  developed,  expanded,  and  controlled 
the  destinies  of  the  world  for  a  thousand  years.  But,  like  many 
normal  individuals  who  live  lives  of  aggression  and  domination, 
they  had  some  psychopathic  and  perilous  periods,  due  to  their  natu- 
ral characteristics. 

The  Romans  started  as  a  race  of  fighting  farmers,  and  at  the 
beginning,  waged  war  mainly  on  the  defensive.  In  order  to  retain 
their  homes  and  land,  they  developed  the  sturdy  virtues  of  disci- 
pline, valor,  and  obedience.  They  were  only  fairly  intelligent,  but 
they  believed  that  they  had  superior  qualities  and  were  extremely 
confident  of  themselves.  They  were  not  strongly  individualistic  like 
the  Greeks,  but  were  willing  to  make  personal  sacrifice  for  the  sake 
of  the  whole  group. 

They  had  an  un  imaginative  state  religion,  and  they  prayed  for 
their  families  and  crops.  They  were  not  a  sensitive  people,  not  gener- 
ous in  spirit,  were  poor  in  emotion,  with  no  great  social  gifts.  They 
had  little  ingenuity,  and  until  later  developed  no  art  or  science — 
except  those  of  war  and  farming. 

Says  Mr.  Jerome  in  "Roman  Memories,"  referring  to  the  early 
Romans: 


A  PSYCHOTIC  EPISODE  IN  ROMAN  HISTORY     701 

"The  Romans  were  a  people  relatively  deficient  in  sentiment  and 
imagination;  intellectually,  they  were  not  above  mediocrity;  they  were 
self-confident,  avaricious,  severe,  and  pitiless,  but  were  not  needlessly 
cruel;  they  were  remarkably  free  from  envy,  hatred,  and  malice;  they  had 
a  strong  feeling  for  gravity  and  decorum,  and  possessed  to  a  degree  higher 
than  in  the  case  of  other  ancient  peoples  the  sentiment  of  justice. 

"They  had  common  sense,  but  no  great  mental  nimbleness,  nor  clar- 
ity of  vision.  They  were  conservative,  credulous,  opportunist,  formalist. 
These  qualities  were  joined  to  their  defective  imagination  and  insight. 
Their  strongest  characteristic  was  their  volitional  power;  they  were  iron- 
willed,  energetic,  determined,  patient,  and  self-controlled.  Their  leaders 
were  not  afraid  to  lead,  and  the  masses  were  not  impatient  of  restraint, 
not  disinclined  to  obey  nor  backward  in  facing  death  or  pain." 

Says  Smith  in  "History  of  Rome'*; 

"We  may  trace  the  superiority  of  the  Romans,  first  to  the  strength 
and  firmness  of  their  character,  which  endowed  them  with  confidence  in 
themselves,  still  more  with  confidence  in  one  another;  to  the  power  of 
command  over  themselves  and  not  less  of  command  over  others;  to  the 
mutual  sympathy  and  brotherly  feeling  nurtured  by  the  perils  they  had 
encountered  and  the  triumphs  they  had  won  together,  and  to  a  conscious- 
ness of  natural  fitness  to  rule  and  an  imperial  destiny  to  accomplish. 
The  vaunted  patriotism  of  the  Romans,  which  was  undoubtedly  both  sin- 
cere and  active,  may  be  resolved  into  a  sense  of  dependence  upon  one 
another  and  an  independence  of  all  besides,  which  taught  them  to  regard 
their  city  as  the  center  of  their  universe." 

The  Romans  prospered.  As  they  became  more  experienced  and 
realized  the  resources  and  enjoyments  of  a  larger  life,  they  secured, 
through  their  primitive  virtues,  their  intelligence  and  practical 
training,  the  things  that  art  and  greater  social  development  in  other 
countries  could  furnish.  They  bought  art  and  culture  and  good 
living.  They  found  it  easier  to  plunder  than  build,  so  they  became 
predatory  in  habit,  and  war  was  used  to  enrich  their  homes  with 
everything  that  the  world  could  furnish. 

They  could  not  fight  and  plunder  and  keep  their  acquisitions 
without  retaining  their  discipline  and  all  that  went  to  make  success- 
ful warriors.  As  they  had  continually  to  fight  not  only  to  acquire 
wealth,  but  to  defend  themselves  against  other  robbers,  they  were 
led  to  become  efficient  in  constructing  roads,  fortresses,  and  buildings. 


702      A  PSYCHOTIC  EPISODE  IN  ROMAN  HISTORY 

They  retained  their  pride  and  egotism,  which  showed  itself  in 
an  intense  desire  to  dominate  and  to  fear  any  form  of  personal  or 
national  enslavement. 

For  about  250  years,  under  the  Kings,  the  Roman  people  were 
busy  organizing  themselves  and  establishing  their  city,  pursuing 
agriculture,  and  defending  themselves  against  their  neighbors. 
Then  the  republic  began,  and  with  it  the  beginnings  of  the  Great 
Addiction.  Rome  began  to  expand;  it  felt  the  desire  for  power,  and 
this  gave  it  plunder,  a  great  commerce,  and  riches.  It  conquered 
Sicily,  parts  of  Spain,  and  all  of  Italy.  At  about  the  same  time  it 
destroyed  Carthage  and  conquered  Greece,  and  by  165  b.  c.  became 
master  of  the  whole  Mediterranean  basin.  Later  this  people  com- 
pleted the  conquest  of  Africa,  Sulla,  Marius,  and  Brutus  plundered 
the  East  and  Spain,  while  Caesar  plundered  Gaul.  When  the  latter 
was  assassinated  he  was  planning  to  conquer  the  Parthians  and  pay 
the  debts  of  the  Romans.  The  desire  for  power  and  territory  and 
money  grew,  as  does  the  desire  for  opium.  The  more  they  possessed, 
the  more  they  needed  to  defend  what  they  possessed.  At  first  this 
was  an  ambition  of  the  people  or  nation,  a  group  ambition,  but  later 
it  became  an  individual  ambition.  It  was  specialized,  and  the 
leaders  or  the  classes  sought  power  and  riches  for  themselves.  This 
led  to  civil  wars:  the  wars  of  the  Gracchi,  of  Sylla  and  Marius, 
the  wiping  out  of  the  Samnites,  and  the  control  of  all  Italy. 

The  nation  was  on  the  point  of  falling  to  pieces  through  the 
debts  and  exhaustion  of  the  state,  the  rivalry  and  ambitions  of  the 
leaders,  and  the  neglect  and  incapacity  of  its  administration. 

Here  is  the  Roman  experience  from  264  b.  c.  to  48  b.  c. 

War  by  Hannibal,  first  Punic  War,  264-241  b.  c;  second  Punic  War, 
218-201  B.  c;  conquest  of  Greece,  200-195  b.  c;  conquest  of  Syria,  Spain, 
and  Cisalpine  Gaul,  191-178  b.  c;  Macedonian  War,  168  b.  c;  final  con- 
quest of  Greece,  148  b.  c;  destruction  of  Carthage,  146  b.  c;  civil  wars 
led  by  the  Gracchi,  133  and  121  b.  c. 

Defensive  and  ofi"ensive  war  against  the  Teutons  and  Jugurtha,  1 10- 
lOi  B.  c;  social  war  led  by  Marius,  90-86  B.C.;  foreign  and  civil  war 
conducted  by  Sulla,  86  to  82  b.  c;  Gallic  wars  by  Caesar,  57  to  48  b.  c; 
conquest  of  the  East  by  Brutus. 

The  condition  of  Rome  at  this  period  is  summed  up  by  Fowler 
somewhat  as  follows:  There  had  been  a  sudden  increase  in  wealth 


A  PSYCHOTIC  EPISODE  IN  ROMAN  HISTORY      703 

which  was  misused  and  misspent,  so  that  the  nation  was  over- 
whelmed with  debt.  There  was  an  abnormal  increase  of  badly  used 
slave  labor;  city  life,  greatly  developed,  was  not  wisely  handled; 
wholesome  family  life  had  decayed;  there  was  a  decadence  of  women 
and  of  the  old  forms  of  state  religion;  the  methods  of  education 
were  wrong,  and  there  had  occurred  an  increase  of  disease,  due  to 
malaria  in  the  country,  to  bad  sanitary  conditions  in  the  city. 

In  Appian's  "Roman  History,"  Book  II,  Sect.  19,  we  are  told 
that  the  Commonwealth  had  for  a  long  time  been  disorderly  and 
unmanageable.  The  magistrates  were  chosen  by  means  of  money 
and  factional  fights.  Bribery  and  corruption  prevailed  in  the  most 
scandalous  manner.  The  people  went  bought  to  the  elections.  The 
Consuls  could  not  lead  armies  or  command  in  war,  because  they  were 
shut  out  by  the  Triumvirate.  The  Republic  went  without  Consuls 
for  eight  months.  Good  men  would  not  take  the  task.  Finally  mob 
violence  broke  out  and  Pompey  was  made  Dictator,  but  his  reforms 
were  short-lived.  A  devotion  to  personal  or  clique  ambitions  had 
taken  the  place  of  loyalty  to  the  government  and  love  of  the  father- 
land. The  condition  has  been  characterized  as  the  beginning  of  na- 
tional degeneracy  and  decline.  But  the  work  of  Rome  in  the  next 
three  centuries  disproves  this. 

It  was  rather  a  psychotic  episode,  precipitated  by  the  weakening 
eflfect  of  wars,  and  excited  finally  by  the  enormous  opportunities 
for  personal  self-indulgence,  so  that  those  things  which  should  have 
gone  to  enrich  and  develop  the  state  went  to  demoralize  and  con- 
fuse the  people. 

When  addiction  overwhelms  an  individual,  there  result  mental 
confusion,  delirium,  clouding  of  consciousness,  and  a  definite  toxic 
exhaustive  psychosis,  calling  for  the  offices  of  a  physician  or  cus- 
todian. 

It  so  happens  that  we  have  a  picture  of  the  times  at  this  period, 
as  accurate  and  vivid  as  if  it  were  a  product  of  the  best  kind  of 
modern  daily  journalism.  This  is  in  the  letters  of  Cicero,  covering 
the  period  50  to  47  b.  c,  in  which  latter  year  Caesar  crossed  the 
Rubicon  and  later  conquered  Pompey  at  Pharsalia. 

Cicero  pictures  the  situation  as  hopeless  if  Caesar  wins.  Historians 
agree  that  it  would  have  been  hopeless  if  he  had  not. 

The  letters  show  Cicero's  views  on  the  instability  of  the  Republic, 


704     A  PSYCHOTIC  EPISODE  IN  ROMAN  HISTORY 

the  power  of  one  general,  the  weakness  of  another.  His  letters  portray 
the  general  distrust  of  those  in  authority  and  a  despair  for  the  future 
of  the  state  and  himself.  I  quote  especially  his  references  to  Caesar, 
as  showing  how  keenly  he  feared  another  social  war  and  civil  disaster. 
All  that  he  apprehended  did  occur  for  a  time,  but  after  Augustus 
had  finished  his  proscriptions  and  restored  social  order,  the  state 
revived  and  grew  in  strength  and  eflficiency  for  several  hundred 
years. 

In  the  year  50  b.  c.  Cicero  had  just  finished  his  government  of 
Cilicia,  and  he  was  on  his  way  home,  when  he  first  got  news  of 
Caesar's  demands — viz.,  to  be  retained  as  governor  of  Gaul,  and 
later  to  be  elected  consul.  The  Senate  soon  voted  that  if  Caesar  did 
not  resign  he  would  be  declared  a  public  enemy. 

Thereupon  Caesar  crossed  the  Rubicon  (49  b.  c),  and  civil  war 
between  him  and  the  loyalists,  led  by  Pompey,  began.  Pompey  left 
Rome,  fled  to  Brundusium,  the  southern  seaport  of  Italy,  and  thence 
crossed  to  Epirus.  Caesar  seized  the  government  at  Rome,  garrisoned 
Italy,  went  to  Spain,  conquered  the  loyalists  there;  returned  to 
Italy;  then  in  January,  48  b.  c,  he  crossed  to  Epirus,  and  in  August, 
48  B.  c,  won  a  victory  over  Pompey  at  Pharsalia.  The  Roman 
republic  was  ended. 

Caesar  began — and  Augustus  completed — the  medical  treatment 
of  Rome,  bringing  back  the  authority  of  Rome  and  its  patriotism 
and  passion  for  domination,  to  the  government,  and  not  to  groups 
of  individuals. 

Specialization  of  power,  without  co-operation  and  authoritative 
organization,  fails  in  national  life  as  it  does  in  personal  life.  This  is 
the  lesson  drawn  from  the  story  of  the  Great  Addiction. 

[Many  letters  are  omitted  in  order  to  shorten  this  article,  such  as 
give  the  picture  of  Rome  when  Catiline  nearly  succeeded,  and  tell 
the  stories  of  the  lives  of  the  men  of  that  time,  Dolabella,  Coelius, 
Curio,  Antony,  Clodius,  Milo.  There  were  only  two  real  men  at  this 
period — Cato  and  Caesar.] 

51  B.  c. 
Marcus  Ccelius  to  Cicero: 

With  respect  to  our  present  divisions,  I  foresee  that  the  senate,  together 
with  the  whole  order  of  judges,  will  declare  in  favor  of  Pompey:  and  that 
ail  of  those  of  desperate  fortunes,  or  who  are  obnoxious  to  the  laws,  will 


A  PSYCHOTIC  EPISODE  IN  ROMAN  HISTORY      705 

list  themselves  under  the  banners  of  Caesar.  As  to  their  armies,  I  am 
persuaded  there  will  be  a  great  inequality.  But  I  hop>e  we  shall  have  time 
enough  to  consider  the  strength  of  their  respective  forces,  and  to  declare 
ourselves  accordingly.  ...  In  the  name  of  all  the  gods,  my  dear 
Cicero,  hasten  hither  to  enjoy  the  diverting  spectacle  of  Appius  sitting 
in  judgment  on  extravagance,  and  Drusus  on  debauchery!  It  is  a  sight, 
believe  me,  well  worth  your  expedition. 

'CI  B    C 

Marcus  Ccelius  to  Cicero: 

Meanwhile,  we  are  in  the  humor  here  of  acquitting  all  criminals: 
nothing,  in  truth,  so  base  or  so  villainous  can  be  perpetrated  that  is  not 
sure  of  escaping  punishment.  You  will  perceive  how  wondrously  active 
our  consuls  are  in  their  office,  when  I  tell  you  that  they  have  not  yet  been 
able  to  procure  a  single  decree  of  the  senate,  except  one  for  appointing 
the  Latin  festivals.  Even  our  friend  Curio  has  not  hitherto  acted  with 
any  spirit  in  his  tribunate;  as,  indeed,  it  is  impossible  to  describe  the 
general  indolence  that  has  seized  us.  If  it  were  not  for  my  contests  with 
the  vintners  and  the  surveyors  of  the  public  aqueducts  all  Rome  would 
appear  in  a  profound  lethargy. 

Cicero  to  Marcus  Ccelius: 

You  mentioned  something  of  a  lethargic  inactivity  that  had  seized 
the  republic.  I  rejoiced,  no  doubt,  to  hear  that  you  were  in  a  state  of  such 
profound  tranquillity,  as  well  as  that  our  spirited  friend  was  so  much 
infected  with  this  general  indolence  as  not  to  be  in  a  humor  of  disturbing 
it.  But  the  last  paragraph  of  your  letter,  which  was  written,  I  observed, 
with  your  own  hand,  changed  the  scene,  and  somewhat,  indeed,  dis- 
composed me.  Is  Curio  really,  then,  become  a  convert  to  Caesar?  But, 
extraordinary  as  this  event  may  appear  to  others,  believe  me,  it  is  agreeable 
to  what  I  always  suspected.  Good  gods  I  how  do  I  long  to  laugh  with  you 
at  the  ridiculous  farce  which  is  acting  in  your  part  of  the  world  I 

Athens,  October  16,  50  b.  c. 
Cicero  to  Atticus^  Greeting: 

If  you  have  at  last  received  my  letter  you  will  know  that  I  have  yours 
through  our  friend  Acastus,  and  that  I  am  in  good  spirits  (bono  animo) 
because  Acastus  told  me  of  your  improved  health.  But  I  shivered  myself 
(coborruisse  autem  me)  at  your  news  of  Caesar's  legions.  .  .  .  For  myself, 
I  seem  to  foresee  a  terrific  struggle  (tantam  dimicationem)  unless  the  same 
god  who  saved  us  in  the  Parthian  war  take  pity  on  the  state — even  so, 
such  a  terrific  struggle  as  there  never  has  been  before. 


7o6     A  PSYCHOTIC  EPISODE  IN  ROMAN  HISTORY 

Cicero  to  Atticus,  Greeting:  ^ormi^,  Dec.  5,  49  b.  c. 

I  have  really  no  news,  but  it  soothes  me  to  write  to  you  and  to  read 
your  letters.  (Acquiesco  enim  et  scribens  ad  te  et  legens  tua.) 

My  fears  about  the  republic  are  very  great.  I  have  no  consolation 
except  the  thought  that  if  fortune  bestows  on  Caesar  the  supreme  power 
he  will  not  be  so  mad  as  to  misuse  his  advantages.  If  he  begins  to  run  amuck 
my  fears  are  more  than  I  dare  to  write.  {Quodsi  ruere  coeperit,  ne  ego  multa 
timeo  quae  non  audeo  scrihere.)  But  whoever  conquers  there  will  come  many 
evils  and  no  doubt  a  tyrant. 

FoRMiiE,  March  8,  49  b.c. 

What  a  difficult  and  calamitous  business  I  {Quern  difficultem  planeque 
perditam.)  How  can  Ccesar  keep  from  a  destructive  policy?  It  is  forbidden 
by  his  character,  his  previous  career,  the  nature  of  his  present  enterprise 
and  his  associates.  For  what  a  following  he  has,  what  damned  souls  1  what 
an  abandoned  and  desperate  cause  I  I  foresee  a  massacre  if  he  conquers, 
an  attack  on  the  wealth  of  nations,  repudiation  of  obligations,  recall  of 
exiles,  high  office  for  the  basest  men  and  a  tyranny  intolerable. 

Please  introduce  Terentia  to  the  bankers;  and  send  me  news  of  Tiro, 
as  you  have  done. 

Brundusium,  Nov.  26,  50  b.  c. 

I  arrived  at  Brundusium  Nov.  24th.  Terentia,  who  met  me  in  the  forum, 
told  me  that  your  second  attack  of  quartan  had  passed  ...  I  hope  that  by 
your  prudence  and  temperance  your  health  has  been  restored.  I  have  all 
your  letters,  each  more  delightful  than  the  last.  .  .  . 

Cato  has  treated  me  shamefully  and  spitefully.  He  gave  me  a  high 
character  (which  I  did  not  want)  but  denied  me  a  triumph,  for  which  I 
asked,  and  how  Caesar  exults  over  this  wrong  done  me  by  Cato  I  .  .  . 

I  long  to  answer  all  your  letters;  though  there  is  one  to  which  I  have 
no  answer  to  make,  and  that  is  the  one  dealing  with  the  perils  of  the 
republic.  I  am  very  much  upset  {valde  eram  perturbatus).  What  would  you 
have  me  do? 

From  Letter  to  Tiro. 

A.  U.  704,  49  B.  c. 

But  an  invincible  rage  for  war  had  unaccountably  seized  not  only 
the  enemies,  but  even  those  who  are  esteemed  the  friends,  of  the  common- 
wealth: and  it  was  in  vain  I  remonstrated,  that  nothing  was  more  to  be 
dreaded  than  a  civil  war.  Caesar,  in  the  mean  time,  unmindful  of  his  former 
character  and  honors,  and  driven,  it  should  seem,  by  a  sort  of  frenzy,  has 
taken  possession  of  Ariminum,  Pisaurum,  Ancona,  and  Arretum. 


A  PSYCHOTIC  EPISODE  IN  ROMAN  HISTORY     707 

From  Letter  XI I,  To  Servius  Sulpicius. 

A.  U.  C.  704,  49  B.  c. 

The  flames  of  war,  you  see,  have  spread  themselves  throughout  the 
whole  Roman  dominions,  and  all  the  world  has  taken  up  arms  under  our 
respective  chiefs.  Rome,  in  the  mean  time,  destitute  of  all  rule  or  magis- 
tracy, of  all  justice  or  control,  is  wretchedly  abandoned  to  the  dreadful 
inroads  of  rapine  and  devastation.  In  this  general  anarchy  and  confusion,  I 
know  not  what  to  expect;  I  scarcely  know  even  what  to  wish.  .  .  . 

From  Letter  XIV ^  Cicero  to  Marcus  Ccelius. 

A.  U.  C.  704,  49  B.C. 

The  truth  of  it  is,  there  is  no  calamity  so  severe  to  which  we  are  not 
all  of  us,  it  should  seem,  in  this  universal  anarchy  and  confusion,  equally 
and  unavoidably  exposed.  But  if  I  could  have  averted  this  dreadful  storm 
from  the  republic  at  the  expense  of  my  own  private  and  domestic  enjoy- 
ments, even  of  those,  my  friend,  which  you  so  emphatically  recommend 
to  my  care,  I  should  most  willingly  have  made  the  sacrifice. 


THE  SCHEMATIC  DRAWING  OF  THE  EYE  IN  ITS 
HISTORIC  DEVELOPMENT 

(fifteenth  and  sixteenth  centuries) 

By  Mortimer  Frank,  S.B.,  M.D.,  Chicago,  III.^ 

THE  difficulties  encountered  in  examining  an  eye  anatomically 
in  earlier  times  probably  led  every  auditor  to  form  his  own 
conception  of  that  which  was  orally  presented  to  him.  These 
concepts  naturally  must  have  been  very  different,  and  so  drawings 
were  made  for  teaching  purposes,  some  of  which  have  been  pre- 
served. These  have  been  carefully  studied  by  Sudhoff. 

Sudhoff's  investigations  commence  with  an  anonymous  Anatomia 
oculi  on  the  back  page  of  a  thirteenth  century  MS.  in  the  Sloane 
collection  of  the  British  Museum  (420).  The  eyeball  and  its  tunics 
are  shown  as  made  up  of  circles  and  divided  perpendicularly  by 
two  straight  lines  into  an  anterior  (left)  and  a  posterior  (right)  half. 
Below  the  figure,  at  the  left,  appears  pars  oculi  exterior;  at  the  right, 
pars  oculi  interior.  The  innermost  circle,  which  is  not  divided,  is 
inscribed  bumor  cristallinuSt  and  the  inscriptions  from  within  out- 
ward in  the  hemispheres  surrounding  this  are  for  the  anterior  half 
(pars  exterior)  as  follows:  tunica  aranea^  bumor  albugineu^,  tunica 
vuea  (uvea),  tunica  cornea^  and  tunica  coniunctiva.  The  tunica  coniunC' 
tiva  has  been  drawn  like  a  perioscopic  lens  which  gradually  thins 
out  towards  the  poles  of  the  eyeball,  an  idea  which  probably  origi- 
nated from  a  misunderstood  drawing  of  the  cornea.  The  posterior 
half  is  inscribed,  reading  from  within  outward,  as  follows:  bumor 
vitreuSf  retbina,  secundina^  tunica  sclirotica.  From  the  upp>er  and 
lower  folds  of  the  eyeball  two  straight  lines  lead  to  the  right  (pars 
posterior)  and  intersect  at  an  acute  angle  (the  limits  of  the  orbit?) 
and  at  their  point  of  intersection  is  written.  Hie  tanget  cerebrum; 
that  is,  the  place  of  entering  the  brain.  From  the  equator  of  the 
posterior  half  to  the  p>oint  of  intersection  of  the  two  straight  lines  is 
the  inscription,  Nervus  opticus,  without  any  linear  limitation. 

*  Dr.  Mortimer  Frank  died  suddenly  April  21,  1919,  in  his  forty-fourth  year,  at  his 
residence,  1059  Hyde  Park  Boulevard,  Chicago,  III. 

708 


THE  SCHEMATIC  DRAWING  OF  THE  EYE        709 

In  another  Sloane  MS.  (981),  belonging  to  the  second  half  of 
the  fourteenth  century,  there  is  a  short  text  with  an  illustration  per- 
taining to  ophthalmic  anatomy.  The  figure  represents  a  cross- 
section  of  the  entire  head,  in  the  center  of  which  is  an  eye  surrounded 
by  circles  and  semicircles,  like  the  coats  of  an  onion.  Here,  as  in  the 
diagram  above,  the  circles  are  divided  by  a  perpendicular  line  into 
an  anterior  and  posterior  part,  with  the  same  inscriptions  as  in  the 
foregoing.  Behind  the  posterior  part  is  a  moon-shaped  sector  marked 
Cerebruniy  surrounded  by  three  semicircular  segments  inscribed  with 
the  names  of  the  coverings  of  the  brain. 

The  Vatican  Library  at  Rome  possesses  the  Codex  Urbinus 
(246),  a  MS.  written  in  the  second  half  of  the  fourteenth  century 
or  the  beginning  of  the  fifteenth,  including  among  its  contents  the 
anatomy  of  Mundinus.  Where  the  structure  of  the  eye  is  discussed, 
a  later  owner  drew,  on  the  margin  of  the  page,  a  diagram  of  the 
arrangement  of  the  coats  of  the  eye  in  the  manner  already  described 
and  with  the  same  inscriptions  within  the  circles. 

Chronologically  following  the  preceding  pictures  is  one  in  the 
Codex  Leipzig  (1183)  ascribed  to  the  first  half  of  the  fifteenth 
century.  Sudhoff  does  not  agree  with  Hirschberg  of  Berlin  that  this 
diagram  should  be  ascribed  to  the  Spanish-Arabian  ophthalmologist 
Alcoati.  This  hasty  pen.  and  ink  sketch  of  the  fifteenth  century 
upon  the  margin  of  a  page  was  copied  from  some  unknown  source. 
The  evidence  is  proof  of  the  fact  that,  independent  of  Arabic  tradi- 
tion, a  cross-section  of  the  eyeball  must  have  been  handed  down 
during  the  Middle  Ages  through  the  Occident.  He  also  points  out 
that  the  placing  of  the  cornea  outside  the  conjunctiva  is  directly 
contrary  to  Alcoati.  Alcoati  did  nothing  original  in  ophthalmology 
and  surely  not  in  his  anatomy.  The  latter  originated  with  the  Greeks 
and  from  them  passed  to  the  Arabs  and  thence  to  the  Occident,  and 
to  Salerno  and  other  medical  schools  through  many  diff"erent  chan- 
nels, and  finally  also  through  the  Latin  translations  from  the  Arabs. 
The  Arabs  made  no  anatomic  investigations  of  their  own  on  the  eye, 
just  as  they  made  none  on  any  other  parts  of  the  body.  The  many 
religious  restrictions  made  the  publication  of  drawings  representing 
parts  of  the  human  body  absolutely  impossible  or  highly  difficult. 
But  even  as  other  diagrams  and  sketches  of  organs  were  made  in 
Alexandria,  so  there  can  be  no  doubt  whatever  that  diagrammatic 


710       THE  SCHEMATIC  DRAWING  OF  THE  EYE 

drawings  of  the  structure  of  the  eye  were  made  there  and  found  their 
way  during  the  Middle  Ages  to  the  Orient  and  Occident.  On  the  other 
hand,  we  have  no  proof  that  all  the  pictures  of  the  eye  which  are 
found  in  the  Latin  editions  of  Arabic  authors  come  from  Arabic 
tradition.  SudhofF  does  not  doubt  that  the  Arabs  possessed  Greek 
diagrams  of  the  eye  in  graphic  form,  but  no  MS.  of  any  Arabic 
work  during  the  Islamic  zenith  contains  a  drawing  of  the  eye. 

During  the  second  half  of  the  thirteenth  century,  the  decline 
of  Islam,  the  Syrian  Halifa  wrote  a  treatise  on  ophthalmology  of 
which  two  MSS.  are  known.  The  drawing  in  the  Constantinople 
MS.  (924)  of  the  sixteenth  century  illustrates  the  structure  of  the 
eye  and  its  connection,  by  means  of  the  chiasm,  with  the  brain.  This 
picture,  published  several  times  without  text  by  Hirschberg,  dates 
from  the  Halifa  MS.  of  the  year  1560. 

Another  interesting  drawing  of  the  eye,  which  also  shows  a  hori- 
zontal cross-section  divided  into  an  anterior  and  posterior  portion 
by  a  median  line,  as  in  the  Occidental  models,  is  found  in  an  Arabic 
MS.  (3008)  in  the  Bibliotheque  Nationale  at  Paris,  written  in  17 14. 
This  is  a  very  late  transmission  if  we  consider  that  the  portion  on 
the  eye  by  the  Syrian,  Salah-Ad-din,  is  said  to  have  been  written 
about  the  year  1296.  The  drawing  was  first  published  by  Pansier 
and  later  again  by  Hirschberg,  but  without  the  anatomic  text  which 
Sudhoff  gives.  It  illustrates  the  combination  of  two  cross-sections 
of  the  globe  perpendicular  to  one  another,  and  plays  even  to-day  a 
certain  r6Ie  in  the  Arabic  world  according  to  Hirschberg.  Sudhoff 
does  not  agree  with  Hirschberg's  interpretation  of  the  picture,  which 
is  of  no  consequence  in  this  discussion.  Whether  it  was  the  original 
illustration  for  Salah-Ad-din's  text  book,  and  as  such  inserted  about 
the  year  1296,  or  whether  it  was  drawn  without  any  influence  from 
the  Alexandrian  or  even  Byzantine  sources,  Sudhoff  is  not  prepared 
to  say. 

Further  researches  might  establish  for  these  graphic  representa- 
tions of  the  structure  of  the  eye  an  earlier  date  than  the  year  1300, 
beyond  which  none  of  the  present  illustrations  go.  Earlier  drawings 
by  Hobeisch  of  the  ninth  century  and  by  Hammar  of  the  eleventh 
century  have  not  been  preserved,  as  far  as  recent  researches  have 
gone.  The  assumption  might  also  be  made  that  all  these  drawings 
found  their  models  in  a  late  Alexandrian  period,  which  remained 


THE  SCHEMATIC  DRAWING  OF  THE  EYE        711 

alive  in  the  traditions  of  the  Orient  and  Occident  far  into  the 
fifteenth  century,  if  not  longer,  and  which  appear  to  have  been  not 
without  influence  even  upon  Leonardo  and  Vesalius. 

The  oldest  printed  illustration  of  the  structure  of  the  eye  is 
found  in  the  "Margarita  Philosophica"  by  Gregor  Reisch,  published 
by  Kaspar  Schott  at  Strasburg  on  April  17,  1504.  The  external  view 
of  the  eye  on  the  same  page  is  a  revised  reproduction  by  Johannes 
Peyligk  and  Magnus  Hundt.  The  Freiburg  Carthusian  monk,  Sud- 
hoff  says,  undoubtedly  got  his  drawing  from  tradition,  as  with  most 
of  the  other  illustrations  in  his  book. 

With  this  early  accessible  model  created  in  the  various  editions 
of  the  "Margarita  Philosophica,"  it  found  a  place  in  other  works,  as, 
for  instance,  Hieronymus  Brunschwig's  "Distilierbuch."  Very  soon 
afterward  it  is  found  in  many  ophthalmic  treatises,  with  alterations 
and  additions.  Independent  modifications,  however,  are  first  ob- 
served in  a  rather  similar  illustration  which  Walther  Reifif  uses  in 
his  "Anatomie"  (154 1).  However  incomplete  the  illustration  still 
is,  there  already  appears  a  trace  of  some  independent  anatomic  ob- 
servation, some  real  study  of  nature.  Reiff^'s  picture  of  the  eye  had 
a  long  life  and  was  reproduced  by  Anton  Novarinus  as  late  as  1681. 

Individual  conception  does  not  come  to  the  surface  until  the 
publication  of  the  "Fabrica  humani  corporis"  by  Andreas  Vesalius 
in  1543.  His  drawing  is  not  wholly  true  to  nature,  especially  as 
regards  the  crystalline  lens.  Vesalius  could  not  free  himself  from  the 
tradition  that  the  crystalline  lens  had  its  seat  in  the  center  of  the  eye, 
a  fact  which  he  particularly  illustrates  in  several  detailed  drawings. 

In  some  respects  it  must  be  admitted  that  before  this,  through 
his  own  individual  observations,  Leonardo  da  Vinci  had  come  nearer 
the  truth  than  any  of  his  predecessors  or  his  successors  up  to  the 
time  of  Vesalius.  He  not  only  treats  of  the  anatomy  of  the  eye,  but 
also  considers  it  from  the  viewpoint  of  optics. 

George  Bartisch,  in  his  treatise  of  1583,  employs  a  schematic 
representation  of  the  eye  made  up  of  seven  superimp)osed  plates, 
a  common  device  of  the  fugitive  anatomical  pictures  of  the  period. 
From  this  it  was  only  a  step  to  the  models  in  three  dimensions  which 
sprang  up  in  the  seventeenth  and  were  common  in  the  eighteenth 
century.  These  were  again  abandoned  for  the  actual  eyes  of  dead 
animals,  still  employed  in  the  teaching  of  to-day. 


PHYSICIANS'   LETTERS 
By  Fielding  H.  Garrison,  M.D.,  Washington,  D.  C. 

ONE  of  the  earliest  modes  of  conveying  medical  information 
known  to  physicians  was  by  means  of  letters,  personal  or 
professional.  These,  in  a  much  later  period,  were  destined 
to  be  the  originals  of  our  medical  periodicals  and  transactions.  From 
the  existence  of  two  pediatric  epistles  from  the  physician  Arad- 
Nana  to  the  Assyrian  king  Assurbanipal  (884-860  B.C.)  on  eye 
trouble  and  epistaxis  in  the  little  prince,  his  son,  one  might  almost 
venture  to  infer  the  possibility  of  clinical  correspondence  between 
physicians  themselves,  as  in  the  old  medieval  Consilia  (consultations 
by  letter).  Morgagni's  "De  sedibus,"  1761,  is,  of  course,  the  most 
remarkable  medical  treatise  in  which  the  consilium  is  consciously 
used  as  a  norm  or  mode  of  expression.  From  the  days  of  Gentile 
da  Foligno  and  Montagnana,  it  is  a  far  cry  to  the  huge  interchange 
of  letters  between  Bretonneau  and  his  pupils  Trousseau  and  Velpeau, 
the  last  and  latest  specimens  of  consilia.  With  the  letters  of  Gui 
Patin  (1601-72),  things  take  a  new  turn.  They  are  a  vast  gossip- 
shop  and  school-for-scandal,  replete  with  the  anecdotage  and 
midisance  usually  associated  with  our  profession.  As  we  approach 
our  own  period,  with  its  mania  for  smartness  and  efficiency,  its 
multiplicity  of  labor-saving  devices  and  its  corresponding  lack  of 
large  leisure  for  anybody,  physicians'  letters  become  dryer  and  more 
businesslike,  with  only  a  touch,  here  and  there,  of  the  Pepysian 
quality.  Delightful  exceptions  are  the  Billroth  letters,  mainly 
rhapsodies  about  music.  Only  passing  reference  can  be  made  to  the 
various  collections  of  Tissot,  Frank,  Scarpa,  Jenner,  Astley  Cooper, 
von  Baer,  PirogofiF,  Korsakoff,  and  others.  The  life  and  letters  of 
Weir  Mitchell  will  be  a  stately  biography,  which  awaits  its  author. 
Almost  every  biography  of  recent  date  is  eked  out  by  means  of 
letters.  Those  of  John  S.  Billings  are  a  fair  example  of  the  modern 
tendency.  His  youthful  letters,  especially  those  from  Civil  War 
battlefields,  are  spirited  and  colorful;  in  the  later  period,  they  are 

712 


PHYSICIANS'  LETTERS  713 

the  plain  business  statements  of  one  who  has  acquired  the  outlook 
of  Stendhal's  ideal  philosopher — to  see  things  as  they  are,  with  the 
clear,  cold  vision  of  a  banker.^ 

In  the  earlier  days  of  the  Surgeon  General's  Library,  Billings 
began  to  gather  from  his  own  extensive  correspondence  a  small 
library  collection  of  autograph  letters  of  notable  physicians.  This 
collection  has  been  very  materially  enlarged  by  liberal  and  valuable 
donations  from  Dr.  A.  Jacobi,  Sir  Lauder  Brunton,  and  others. 
Brunton  began  his  correspondence  with  the  writer  in  the  following 
letter,  which  may  be  embalmed  in  this  keepsake  as  afifording  an 
interesting  view  of  Huxley's  ultimate  attitude  towards  religion. 

"May  5,  1915. 
"I  have  been  reading  with  great  delight  the  charming  memoir  you 
have  written  of  my  dear  old  friend  Dr.  John  Shaw  Billings.  I  trust  you 
will  forgive  me  if  I  write  to  you  in  regard  to  a  mistake  you  have  made  in 
what  you  say  regarding  another  dear  friend  of  mine,  the  late  Thomas 
Henry  Huxley.  At  page  373  you  say  on  the  questions  of  religion  and 
immortality  of  the  soul,  Huxley's  attitude  was  antagonistic.  I  knew  Huxley 
very  well,  indeed,  and  for  a  long  time  spent  my  Sunday  evenings  generally 
at  his  house  in  Marlborough  Road,  where  he  and  Mrs.  Huxley  had  a 
'high  tea'  every  Sunday  night,  to  which  they  welcomed  any  of  their 
friends  who  might  drop  in  without  any  formal  invitation.  I  had  been 
brought  up  in  one  of  the  straitest  sects  of  Scotch  Presbyterianism,  and 
the  Bible  being  the  most  interesting  of  the  four  or  five  books  which  I 
was  permitted  to  read  on  the  Sabbath,  I  naturally  learned  to  know  it 
well — so  well  indeed  that  I  have  only  met  two  men  in  my  Hfe  who,  I 
thought,  knew  it  better  than  I  did,  and  one  of  these  was  Thomas  Henry 
Huxley.  Some  of  his  opponents  objected  to  his  use  of  Biblical  phraseology, 
but  he  used  it  simply  because  he  was  so  steef>ed  in  the  language  of  the 
Bible  that  he  could  not  help  it.  But  it  was  not  the  language  of  the  Bible 
only  that  Huxley  knew.  He  had  assimilated  its  teachings  and  guided 
his  life  by  them.  Huxley  has  always  apF>eared  to  me  as  one  of  the  most 
religious  men  I  have  ever  met.  He  was  pugnacious  by  nature  and  detested 
Pharisees  intensely,  but  I  do  not  think  that  in  all  his  writings  you  will 
find  such  strong  language  about  them  as  that  in  the  Gospel  of  Matthew, 
Chap,  xxiii,  13,  14  and  15. 

'  Pour  £tre  bon  philosophe,  il  faut  6tre  sec,  clair,  sans  illusion.  Un  banquier  qui  a 
fait  fortune  a  une  partie  du  caractfere  requis  pour  faire  des  d6couvertes  en  philosophic, 
c'est  k  dire  pour  voir  clair  dans  ce  qui  est." — Stendhal. 


714  PHYSICIANS'  LETTERS 

"In  1879  I  married  a  daughter  of  the  late  archdeacon  of  Meath. 
Shortly  after  our  return  from  our  honeymoon  we  went  together  to  Huxley's 
one  Sunday  night.  He  took  my  wife  a  little  apart  and  began  to  ask  her 
about  herself.  When  she  told  him  that  she  was  a  clergyman's  daughter 
he  asked  about  me.  When  she  said,  'Dr.  Brunton  is  a  Presbyterian'  he 
drew  himself  up  involuntarily  and  said — not  without  some  pride,  my  wife 
thought — 'We  were  all  Church  of  England  people.* 

"His  natural  turn  for  argument  was  fostered  by  his  father,  who  set 
all  his  boys  two  and  two  at  a  time  to  argue  a  question.  At  the  end  of  half 
an  hour  they  had  to  change  sides  and  demolish  the  view  they  had  at 
first  taken  as  best  they  could.  When  I  tell  you  farther  that  after  his  death 
Mrs.  Huxley  told  me  that  he  had  been  buried  at  his  own  special  request 
with  the  full  Church  of  England  service,  I  think  you  will  agree  with  me 
that  his  attitude  regarding  the  questions  of  religion  and  the  immortality 
of  the  soul  cannot  properly  be  described  as  'antagonistic* 
"Believe  me, 

"  Faithfully  yours, 

"Lauder  Brunton.'* 

Toward  the  end  of  his  life,  Brunton  began  to  send  to  the  Surgeon 
General's  Library  many  gifts  of  unique  value,  among  them  his 
choice  collection  of  autograph  letters  of  notable  physicians.  These 
were  accompanied  by  extensive  commentaries,  written  out  by 
himself.  A  few  paragraphs,  of  historical  and  biographical  interest, 
are  worth  quoting: 

"  September  27,  1915. 

"...  I  am  sending  you  a  batch  of  autographs:  some  are  interesting 
others  are  of  no  particular  interest. 

"You  have  probably  a  very  large  number  of  Acland's  letters  in  the 
correspondence  he  had  with  Billings,  because  they  were  very  fond  of  each 
other,  but  the  one  that  I  send  you  is  interesting  because  Acland  has  put 
in  it  very  shortly  the  dream  of  his  life  to  make  Oxford  a  University  for  the 
advancement  of  learning  rather  than  for  its  dissemination.  For  a  good  many 
years  I  examined  in  Materia  Medica  in  Oxford  and  during  the  period 
of  examination  I  was  always  his  guest.  On  one  occasion  a  curious  incident 
occurred  which  showed  that  Acland  possessed  to  a  very  extraordinary 
degree  indeed  the  power  of  foreseeing  other  people's  intentions.  It  almost 
outdid  any  of  Sherlock  Holmes'  adventures.  I  was  going  to  the  examination 
one  hot  afternoon  and  I  must  have  been  drowsy.  I  looked  out  at  Oxford 
Station  but  did  not  see  the  name,  and  on  the  contrary  saw  in  very  large 
characters  the  name  of  Reading,  which  I  afterwards  found  out  belonged 


PHYSICIANS'  LETTERS  715 

to  an  advertisement  of  Reading  Ales.  I  did  not  get  out  but  at  the  next 
station  looked  up  and  saw  that  I  had  passed  Oxford  and  got  on  to  Ban- 
bury. I  knew  the  students  would  all  be  waiting  for  me  and  I  was  much 
perturbed.  I  found  that  the  only  way  of  getting  back  to  Oxford  was  to 
wait  for  two  hours,  which  of  course  was  far  too  long,  or  else  to  take  a  special 
train  back.  I  at  once  got  a  special  train  and  on  arriving  at  Oxford  Station 
on  the  up  platform,  to  my  astonishment,  I  found  Sir  Henry  Acland  waiting 
for  me.  I  asked  him  how  this  came  about.  He  said,  *I  knew  you  had  left 
London,  for  if  you  had  not  you  would  have  sent  a  telegram.  I  knew  you 
had  passed  Oxford,  because  you  did  not  get  out.  I  knew  you  would  find 
out  your  mistake  and  take  a  special  train  back  and  here  you  are.*  He  said, 
*I  told  the  boys  that  you  had  been  detained  and  I  kept  them.  They  are  all 
waiting  in  the  Examination  Hall.*  We  went  back  to  the  Examination  Hall, 
the  examination  began  about  half  an  hour  late  but  otherwise  as  if  nothing 
had  happened.  The  special  train,  however,  consumed  almost  the  whole 
of  my  salary  as  examiner  for  the  year  at  Oxford.  .  .  .  Heidenhain's  letter 
refers  to  certain  statements  made  by  Lawson  Tait.  He  said  that  Harvey 
had  not  discovered  the  circulation  of  the  blood  by  means  of  vivisection. 
Harvey  himself  said  that  he  had  but  Harvey  was  dead  and  could  not  con- 
tradict Lawson  Tait;  but  Lawson  Tait  went  on  quite  unnecessarily  to 
say  that  this  had  been  admitted  in  their  evidence  by  Sir  Henry  Acland 
and  Dr.  Lauder  Brunton.  Both  these  men  were  alive  and  promptly  con- 
tradicted Lawson  Tait's  statement.   He  searched  the  evidence  but  in 
vain,  for    the    statements    attributed    to    Acland    and    Brunton    were 
not  there.  He  then  said  that  his  informant  was  Mr.  Jesse,  secretary 
of   the    Anti- vivisection    Society.    Mr.   Jesse   said   that   he    had   done 
nothing  of  the  kind,  and  Lawson  Tait  was  left  in  the  lurch.  If  Lawson 
Tait  had  been  content  to  limit  his  statements  to  Harvey  he  would  have 
been  all  right,  but  his  memory  played  him  false  in  regard  to  Acland  and 
me.  Lawson  Tait  was  not  at  all  a  deliberate  liar:  he  simply  did  not  know 
what  truth  was.  He  could  not  distinguish  between  the  products  of  his  own 
imagination  and  objective  facts.  He  was  a  student  of  medicine  in  Edin- 
burgh University  when  I  began  to  study.  He  still  remained  a  student  .when 
I  left,  and  as  far  as  University  was  concerned  he  was  never  anything  but 
a  student  because  he  could  not  pass  the  examinations.  When  he  went  up 
for  examinations  he  gave  what  he  believed  to  be  the  correct  answer  to 
the  questions,  but  unfortunately  these  answers  were  not  what  the  ex- 
aminers wanted.  They  told  him  to  go  back  and  study  for  several  months 
more.  Finally  he  succeeded  in  getting  a  license  from  the  College  of  Surgeons, 
but  he  never  got  a  University  degree.  But  the  same  excessive,  lively 
imagination  which  was  such  an  enemy  to  him  at  examinations  befriended 


7i6  PHYSICIANS*  LETTERS 

him  most  thoroughly  in  debating  societies.  At  the  Royal  Medical  Society 
of  which  I  was  a  member  there  was,  on  one  occasion,  a  special  discussion 
in  regard  to  tracheotomy.  Some  of  the  members  who  were  house  surgeons 
had  had  as  many  as  six  cases.  Lawson  Tait  was  not  a  member  of  the 
Society  but  was  invited  to  come  as  a  guest  and  take  part  in  the  discussions. 
He  got  up  and  stated  that  he  had  had  either  68  or  86  cases,  I  do  not  remem- 
ber which,  he  still  being  a  student  without  any  license  to  practice  at  all. 
Various  members  of  the  Society  expressed  their  incredulity,  but  Lawson 
Tait  was  quite  equal  to  the  occasion  and  proceeded  to  give  all  particulars 
of  cases  with  the  same  minuteness  as  Defoe  employed  in  his  history  of 
Robinson  Crusoe.  After  he  had  given  six  or  eight  most  vivid  accounts  of 
his  operations  and  success  the  Society  thought  they  would  take  the 
remainder  as  read.  .  .  .  There  is  no  particular  interest  in  Laycock's 
letter,  but  the  man  was  very  interesting  personally.  He  had  a  most 
profound  confidence  in  himself  and  I  have  heard  him  say  'Twenty-five 
years  ago,  gentlemen,  I  wrote  a  book  which  was  then  half  a  century  above 
its  age,  but  the  age  is  now  gradually  beginning  to  appreciate  it.*  The  odd 
thing  was  that  in  saying  this  he  understated  the  truth.  The  book  was 
'Nervous  Diseases  of  Women,*  and  such  neurologists  as  Ferrier  and 
Crichton  Browne  still  look  upon  it  as  in  advance  of  the  age.  Laycock  was 
really  the  original  of  Sherlock  Holmes.  Conan  Doyle  got  the  idea  from  Joe 
Bell,  but  Joe  Bell  got  his  ideas  from  Laycock,  who  was  BeII*s  teacher  as 
well  as  mine.  He  used  sometimes  to  make  very  brilliant  diagnoses,  and  at 
others,  great  mistakes.  I  have  known  him  diagnose  waxy  degeneration 
of  the  capillaries  of  the  small  intestine,  and  post-mortem  examination 
proved  the  correctness  of  the  diagnosis.  He  has  also  been  known  simply 
on  walking  through  a  ward  to  look  at  a  man  and  say  'This  patient  has 
cancer  of  the  pancreas.  *  Again  he  was  correct.  One  day  he  was  telling  the 
students  a  great  deal  about  a  child  and  he  said  to  them,  'Gentlemen,  I 
know  all  this  from  my  observation  of  the  mother.*  'Please,  Sir,'  said  the 
woman,  'I  am  only  his  stepmother.*  Another  time  he  was  saying,  'This  I 
can  tell,  gentlemen,  from  the  condition  of  the  patient's  teeth.'  'Please,  Sir, 
shall  I  hand  them  round?'  said  the  patient,  taking  the  teeth  out.   .     .   ** 

John  Hunter's  letters  to  Jenner  are  good  examples  of  the 
circumstantial  notes  of  a  scientific  investigator,  wrapped  up  in 
his  own  subject.  An  amusing  instance  is  the  famous  letter  of 
September  25,  1778,  in  which  Hunter  bluntly  consoles  Jenner  for 
disappointment  in  love,  "Let  her  go,  never  mind  her.  I  shall  employ 
you  with  hedgehogs."  In  the  Brunton  correspondence  there  is  a 
letter  from  Gaskell,  in  which  we  are  taken  into  his  laboratory  and 


PHYSICIANS*  LETTERS  717 

see  the  great  physiologist  at  work  on  his  monograph  on  the  vagus 
nerve. 

"  Grantchester,  Cambridge, 

"Dear  Brunton:  "^P'"  3.  .882. 

"  It  was  very  good  of  you  to  think  of  me  with  respect  to  the  tortoises. 
I  certainly  am  going  on  with  the  vagus  action  and  have  already  made  a 
large  number  of  experiments  on  the  tortoise  and  a  few  on  the  snake; 
every  animal  has  its  own  peculiarities  and  affords  very  interesting  results- 
tortoises  are  specially  good.  I  hop>e  to  work  through  all  the  different 
kinds  of  beasts  I  can  get  and  finally  tackle  the  mammal.  As  to  Meyer's 
tortoise,  I  think  I  have  seen  the  same  thing  to  all  intents  and  purposes 
in  the  ordinary  tortoise.  I  find  the  R  nerve  always  has  more  power  of 
stopping  or  slowing  than  the  L,  while  the  L  often  has  a  more  marked  action 
on  the  strength  of  the  auricular  contractions  than  the  R.  Also  the  separa- 
tion of  fibres  that  slow  and  fibres  which  diminish  and  increase  the  force 
of  the  contractions  is  carried  out  by  nature  in  the  ordinary  tortoise  in  a 
most  excellent  way,  for  the  R  vagus  first  passes  to  the  sinus  and  is  in  con- 
nection with  the  ganglion  cells  there,  then  in  great  part  leaves  the  heart 
to  run  an  isolated  course  along  one  of  the  coronary  veins,  which  passes 
from  the  ventricle  to  the  sinus  entirely  free,  so  that  a  piece  of  nerve  lying 
between  the  ganglia  of  sinus  and  those  in  auric.-ventr.  groove  can  be  iso- 
lated and  stimulated.  The  result  is  that  the  fibres  which  pass  to  the  sinus 
do  all  the  slowing;  those  which  pass  to  the  auric.-ventr.  ganglia  do  the 
diminution  and  increase  of  the  auric,  contractions.  Also,  other  matters  of 
great  interest  have  turned  up,  showing  for  instance  that  the  sequence  of 
vent,  upon  aur.  does  not  depend  on  the  large  nerves  between  sin.  and 
vent,  but  upon  the  auricular  contractions.  Some  of  these  results  I  hope  to 
show  at  Cambridge  and  would  much  like  to  show  them  to  you  and  talk 
them  over. 

"With  kind  regards  to  Mrs.  Brunton, 

"Yours  ever, 

"W.  H.  Gaskell." 

A  note  of  Lister's  refers  to  his  monograph  on  the  cutaneous 
pigmentary  system  of  the  frogs,  one  of  his  preliminary  studies  in 
the  mechanism  of  inflammation. 

"Mv  Dear  Doctor  Lauder  Brunton:  ^     '       ^' 

"My  observations  on  the  pigment  cells  were  published  in  the  Pbila. 
Trans,  for  1859.  May  I  ask  you  to  accept  one  of  the  few  separate  copies 
I  have  left? 


7i8  PHYSICIANS'  LETTERS 

"The  impression  conveyed  to  me  in  observing  the  movements  of  the 
pigment  molecules  was  that  they  were  free  in  a  fluid.  But  we  then  knew 
nothing  about  protoplasm,  and  I  have  often  felt  a  desire  to  observe  the 
phenomena  again  in  the  light  of  our  present  knowledge. 
"Believe  me, 

"Yours  very  truly, 

"Joseph  Lister.** 

There  is  an  interesting  batch  of  letters  interchanged  between  Sir 
Henry  Acland  and  the  late  Dr.  John  S.  Billings,  which  deserves  to 
be  printed  in  part,  if  the  Acland  letters  can  ever  be  entirely 
deciphered.  The  passage  in  the  Acland  note  referred  to  by  Brunton 
(supra)  reads  as  follows: 

"Oxford,  England, 

"July  24,  1 89 1. 
" .  .  .At  last  I  can  see  the  hope  of  the  foundation  here  of  a  general 
comparative  pathology,  one  of  my  lifelong  dreams  for  Oxford,  through 
good  report  and  evil  report.  You  must  all  help  me  to  counteract  the  craze 
here  to  educate  numbers  only  for  the  'M.B.,'  omitting  thereby  all  earlier 
conceptions  of  the  wider  morphology  and  pathology  which  John  Hunter, 
one  would  have  thought,  had  founded  forever, 

"Always  yours, 

"H.  W.  Acland.** 

Among  the  many  unpublished  notes  of  Billings  is  this  breezy 
little  bit  of  chaffing,  one  of  his  humorous  love-taps  to  his  personal 
friends: 

"January  5,  1892. 
"  I  have  yours  of  January  4th.  I  do  not  in  the  least  understand  what 
you  mean  by  acknowledging  the  receipt  of  your  'suspension  in  the  Surgeon 
General's  Department.*  Who  has  been  suspending  you?  What  are  you 
suspended  from?  And  why  do  you  feel  particularly  thankful  about  it? 
"With  the  compliments  of  the  season, 

"Yours  very  sincerely, 

"John  S.  Billings.** 

The  following,  addressed  to  the  Harvard  physiologist.  Professor 
Henry  P.  Bowditch,  deals  with  one  of  the  burning  questions  of  the 
hour,  namely,  the  centralization  of  public  health  in  a  governmental 
bureau.  It  has  the  bold,  straightforward  alter  droit  au  but  which 
was  eminently  characteristic  of  Billings. 


PHYSICIANS'  LETTERS  719 

"February  27,  1892. 
"My  Dear  Dr.  Bowditch: 

"Your  letter  of  February  23d  is  received.  I  do  not  upon  the  whole 
think  that  it  is  desirable  to  attempt  to  create  a  Cabinet  officer  to  be 
known  as  a  'Medical  Secretary  of  Public  Health';  or  that  it  is  expedient 
for  the  medical  profession  to  urge  the  creation  of  such  an  office.  At  best 
it  would  be  held  but  four  years,  and  the  probabilities  of  having  it  filled 
by  a  satisfactory  man  are,  I  think,  extremely  small.  The  benefits  to  be 
derived  from  it  are  very  doubtful.  It  is  the  old  scheme  of  Jeremy  Bentham. 
Such  an  officer,  to  have  any  practical  power,  must  have  more  or  less 
control  of  the  medical  departments  of  the  government,  that  is  to  say,  of  the 
Medical  Departments  of  the  Army  and  of  the  Navy,  of  the  Marine 
Hospital  Service,  the  Indian  Bureau,  the  Pension  Bureau,  of  the  Army 
Medical  Museum  and  the  Naval  Museum  of  Hygiene,  and  so  on.  This  is  a 
concentration  of  powers  and  duties  which  I  feel  very  sure  would  not  be 
expedient  at  the  present  time,  and  it  would  require  a  man  with  the 
qualities  of  an  archangel  to  fill  the  position  satisfactorily.  I  believe  that 
we  ought  to  have  a  National  Board  of  Health,  composed  of  a  limited 
number  of  men,  such  Board  to  be  under  the  direction  of  the  Department 
of  the  Interior,  and  not  of  the  Treasury  Department.  But  this  scheme 
for  a  medical  cabinet  officer  appears  to  me  to  be  utterly  impracticable, 
and  in  fact  hardly  worth  serious  discussion;  and  I  feel  absolutely  certain 
that  no  influence  which  can  be  brought  to  bear  upon  the  present  Congress 
could  induce  the  creation  of  a  new  salaried  office  like  this. 

"With  kindest  regards  and  best  wishes  believe  me  to  be, 

"Very  sincerely  yours, 

"J.  S.  Billings." 


HOMAGE  TO  SIR  WILLIAM  OSLER 
By  Arpad  G.  Gerster,  M.D.,  New  York 

XOPOS 

.  .  .  TTJg  avSpeiag 
Elvexa  Tavrng, 
EvTuxia  YsvoiT*  dv — 

^QWJKp,  OTl  JIQOTJXOV 

'Eg  paOt)  trig  fjXixiag, 
NecoT8Qoig  xfiv  cpvoiv  dvxov 
Ugdyiiaai  XQcoTi^erai 
Kai  CToqpiav  eJtaoxEi. 

Aristophanes,  The  Clouds 

CHORUS 

.   .   .   virtutem 

Ob  hanc 

Feliciter  evenit  huic 

Homfni,  quod  aetate, 

Multum  provecta, 

Recentioribus  ingenium  suum 

Rebus  exornat, 

Et  sapientiam  colit. 

Versio  Stepbani  Bergleri  (1760) 

CHORAL  SONG 

.    .   .   for  virtue's  guerdon 

This  fate  is  vouchsafed  now 

To  yonder  man: 

That  at  the  age 

Of  mellow  ripeness 

His  genius,  through  wisdom's  culture, 

May  freshly  blossom  forth  in  works 

Of  all-surpassing  beauty. 

Paraphrase  by  A.  G.  G. 
7ao 


EPIDEMICS  OF  INFLUENZA  IN  1647, 1789-90  AND  1807 

AS  RECORDED  BY  NOAH  WEBSTER,  BENJAMIN  RUSH,  AND 

DANIEL  DRAKE 


T 


By  Guy  Hinsdale,  M.D.,  Hot  Springs,  Va. 

HE  earliest  record  of  influenza  in  America  was  made  by 
Hubbard,  whose  "Manuscript*'^  informs  us  that: 


'In  the  year  1647  an  epidemical  sickness  passed  through  the  whole 
country  of  New  England  both  among  Indians,  English,  French  and  Dutch. 
It  began  with  a  cold  and  in  many  was  accompanied  with  a  light  fever.  Such 
as  bled,  or  used  cooling  drinks,  generally  died;  such  as  made  use  of  cordials, 
and  more  strengthening,  comfortable  things,  for  the  most  part  recovered. 
"It  seems  to  have  spread  through  the  whole  coast,  at  least  all  the 
English  Plantations  in  America,  for  in  the  Island  of  Christophers  and 
Barbadoes  there  died  5  or  6000  in  each  of  them.  Whether  it  might  be  called 
a  plague  or  pestilential  fever,  physicians  must  determine.  It  was  accom- 
panied in  those  islands  with  a  great  drought,  which  burnt  up  all  their 
potatoes  and  other  fruits,  which  brought  the  provisions  of  New  England 
into  great  request  with  them,  who  before  that  time  had  looked  ujx)n  New 
England  as  one  of  the  poorest,  most  despicable,  barren  parts  of  America."  * 

Noah  Webster,  the  famous  lexicographer,  in  his  "  Brief  History 
of  Epidemic  and  Pestilential  Diseases,"  published  in  Hartford, 
Conn.,  in  1799,  in  two  volumes,  gives  in  chronological  order  a  list 
of  epidemics  of  "influenza  or  epidemic  catarrh,"  dating  in  Europe 
from  a.d.  1 174,  and  in  America  from  1647.  In  this  remarkable  list 
of  44  instances  of  influenza  there  are  most  interesting  notes  of  earth- 
quakes, volcanic  eruptions,  and  comets,  since  it  was  the  fashion  in 
those  days  to  associate  something  supernatural  with  the  outbreak 
of  a  pestilence.  So  we  read  that  the  epidemic  of  1 174  was  "the  year 

*  William  Hubbard's  Manuscript,  Massachusetts  Historical  Society  "Collections," 
2d  Series,  VI,  531,  532.  The  author  is  indebted  to  Mr.  Worthington  C.  Ford  for  the 
transcript. 

*  There  is  a  slight  confusion  here.  According  to  Winthrop  the  drought  preceded  the 
pestilence. — H. 

721 


722  EPIDEMICS  OF  INFLUENZA 

before  an  eruption  of  Etna";  that  of  15 lo  "the  same  year  with  an 
eruption  in  Iceland  and  following  great  earthquakes,  humid  air — a 
comet  appeared  the  next  year";  in  1647,  "First  catarrh  mentioned 
in  American  annals.  The  same  year  with  violent  earthquakes  in 
South  America,  a  comet." 

In  Noah  Webster's  view,  Etna,  Vesuvius,  comets,  and  earth- 
quakes loom  large  in  etiology.  He  states^  in  regard  to  the  epidemics 
listed: 

"i.  That  most  of  them  happened,  after  or  during  severe  cold,  or  during 
moist  weather  and  in  spring,  winter  or  autumn.  Some,  however, 
occurred  in  dry  hot  seasons,  and  others  in  mild  winters. 

"2.  Nineteen  instances  occurred  in  years  when  there  was  a  volcanic 
eruption  in  Italy  or  Iceland,  and  eleven  others,  though  in  different 
years,  were  within  a  few  months  of  eruptions;  making  30  out  of  the 
44.  Two  or  three  others  happened  near  the  time  of  volcanic  discharges 
in  South  America." 

"3.  Almost  all  happened  in  years  of  earthquakes,  or  within  a  few  months 
preceding  or  following  them. 

"4.  Thirty  instances  occurred  within  the  year,  or  a  few  months  preceding 
or  following  the  appearance  of  comets. 
"  It  is  further  to  be  observed  that  some  of  these  epidemics  have  been 

limited  to  the  American  hemisphere,  at  the  distance  of  three,  four  or  five 

years  from  an  epidemic  of  the  same  kind  in  Europe.  Such  as  those  of 

1 647-1 655 — which  coincide  in  time  with  violent  earthquakes  in  South 

America." 

It  is  remarkable  and  worthy  of  record  that  the  epidemic  of 
influenza  which  ravaged  the  Atlantic  coast  shortly  after  the  Revolu- 
tion had  practically  all  the  features  of  the  recent  epidemic.  There 
was  no  better  student  of  clinical  medicine  in  those  days  than  Ben- 
jamin Rush,  who  held  the  chair  of  the  Practice  of  Medicine  and  of 
Clinical  Practice  in  the  University  of  Pennsylvania,  which  a  cen- 
tury later  was  graced  by  Prof.  William  Osier.  Dr.  Rush  had  the 
unusual  faculty  and  patience  to  set  down  the  minute  details  of 
cases  as  they  came  under  observation.  He  was  deeply  interested  in 
the  weather  as  it  aff"ected  the  sick  and  the  \yell,  and  he  urged  his 
students  to  make  a  study  of  meteorology;  this  was  partly  because 
of  the  evident  relation  of  epidemic  diseases  to  atmospheric  condi- 

•11,33-36. 


EPIDEMICS  OF  INFLUENZA  jaj 

tions.  Climatic  influences  always  had  for  him  a  prominent  place  in 
etiology. 

On  turning  to  Rush's  chapter  on  influenza  as  published  in  his 
"  Inquiries  and  Observations,"  one  is  struck  with  a  very  remarkable 
parallel  between  the  course  of  the  epidemic  of  1789  and  1790  and 
that  of  1918  and  19 19.  In  the  account  preserved  to  us  by  Benjamin 
Rush  there  are  many  of  the  familiar  sj'mptoms  so  noticeable  in  the 
last  epidemic. 

Rush  noticed  that  the  epidemic  followed  a  cool  summer  and,  in 
the  early  cases,  occurred  in  those  suff"ering  from  fatigue.  Then  fol- 
lows a  classic  description  of  the  extraordinary  sneezing  with  hoarse- 
ness and  sore  throat;  a  sense  of  weariness,  chills  and  fever,  pains  in 
the  head,  and  abscesses  in  the  frontal  sinus.  Rush  noted  the  watery 
eyes  and  the  occurrence  of  swellings  just  behind  the  ears,  now  recog- 
nized as  the  familiar  mastoiditis.  There  was  the  distressing  cough 
which  in  some  cases  was  moreof  a  tracheitis;  and  the  final  pneumonia. 
He  also  described  the  abdominal  form;  also  the  fact  that  those 
employed  in  out-of-door  occupations,  such  as  'longshoremen,  sur- 
veyors, and  the  Niagara  Indians,  had  it  severely.  He  notes  the  oc- 
currence of  insanity  consequent  on  influenza.  We  wonder  if  Rush 
could  possibly  have  observed  the  eff'ects  of  the  streptococcus  hemo- 
lyticus,  for  he  described  "streams  of  blood"  and  spitting  of  blood 
in  consequence  of  the  violence  of  the  cough. 

Dr.  Rush's  account  is  of  great  historic  interest,  revealing  a 
parallel  between  the  clinical  course  of  these  two  epidemics  separated 
by  129  years;  so  I  am  giving  his  account  in  his  own  words. 

"an  account  of  the  influenza  as  it  appeared  in  PHILADELPHIA 
IN  the  autumn  of  1789,  IN  THE  SPRING  OF  I79O  AND  IN  THE  WINTER 
OF  1 79 1,  FROM  'medical  INQUIRIES  AND  OBSERVATIONS*  BY  BENJAMIN 
RUSH,   M.D.,   PUBLISHED  IN  PHILADELPHIA,    1819. 

"The  latter  end  of  the  month  of  August,  in  the  summer  of  1789, 
was  so  very  cool  that  fires  became  agreeable.  The  month  of  September 
was  cool,  dry,  and  pleasant.  During  the  whole  of  this  month,  and  for 
some  days  before  it  began,  and  after  it  ended,  there  had  been  no  rain. 
In  the  beginning  of  October,  a  number  of  the  members  of  the  first  congress, 
that  had  assembled  in  New  York,  under  the  present  national  government, 
arrived  in  Philadelphia,  much  indisposed  with  colds.  They  ascribed  them 
to  the  fatigue  and  night  air  to  which  they  had  been  exp>osed  in  travelling 


724  EPIDEMICS  OF  INFLUENZA 

in  the  public  stages;  but  from  the  number  of  f>ersons  who  were  affected, 
from  the  uniformity  of  their  complaints,  and  from  the  rapidity  with 
which  it  spread  through  our  city,  it  soon  became  evident  that  it  was  the 
disease  so  well  known  of  late  years  by  the  name  of  the  influenza. 

"The  symptoms  which  ushered  in  the  disease  were  generally  a  hoarse- 
ness, a  sore  throat,  a  sense  of  weariness,  chills,  and  a  fever.  After  the 
disease  was  formed,  it  affected  more  or  less  the  following  parts  of  the 
body.  Many  complained  of  acute  pains  in  the  head.  These  pains  were 
frequently  fixed  between  the  eye-balls,  and  in  three  cases  which  came  under 
my  notice,  they  were  terminated  by  abscesses  in  the  frontal  sinus,  which 
discharged  themselves  through  the  nose.  The  pain  in  one  of  these  cases, 
before  the  rupture  of  the  abscess,  was  so  exquisite  that  my  patient  in- 
formed me  that  he  felt  as  if  he  should  lose  his  reason.  Many  complained 
of  a  great  itching  in  the  eye-lids.  In  some  the  eye-lids  were  swelled.  In 
others,  a  copious  effusion  of  water  took  place  from  the  eyes;  and  in  a  few, 
there  was  a  true  ophthalmia.  Many  complained  of  great  pains  in  one 
ear,  and  some  of  pains  in  both  ears.  In  some,  these  pains  terminated  in 
abscesses,  which  discharged  for  some  days  a  bloody  or  purulent  matter. 
In  others,  there  was  a  swelling  behind  each  ear,  without  a  suppuration. 
.  .  .  Sneezing  was  a  universal  symptom.  In  some,  it  occurred  not  less 
than  fifty  times  a  day.  The  matter  discharged  from  the  nose  was  so  acrid 
as  to  inflame  the  nostrils  and  the  upp>er  lip,  in  such  a  manner  as  to  bring 
on  swellings,  sores,  and  scabs  in  many  people.  In  some,  the  nose  discharged 
drops,  and  in  a  few  streams  of  blood,  to  the  amount  in  one  case,  of  twenty 
ounces.  In  many  cases  it  was  so  much  obstructed  as  to  render  breathing 
through  it  difficult.  In  some,  there  was  a  total  defect  of  taste.  In  others, 
there  was  a  bad  taste  in  the  mouth,  which  frequently  continued  through 
the  whole  course  of  the  disease.  In  some,  there  was  a  want  of  appetite. 
In  others,  it  was  perfectly  natural.  Some  complained  of  a  soreness  in  their 
mouths,  as  if  they  had  been  inflamed  by  holding  pepper  in  them.  Some 
had  swelled  jaws,  and  many  complained  of  tooth-ache.  I  saw  only  one 
case  in  which  the  disease  produced  a  coma. 

"  Many  were  affected  with  pains  in  the  breast  and  sides.  A  difficulty 
of  breathing  attended  in  some,  and  a  cough  was  universal.  Sometimes 
this  cough  alternated  with  a  pain  in  the  head.  Sometimes  it  preceded  this 
pain,  and  sometimes  followed  it.  It  was  at  all  times  distressing.  In  some 
instances  it  resembled  the  chin  cough.  One  person  expired  in  a  fit  of  cough- 
ing, and  many  persons  spat  blood  in  consequence  of  its  violence.  I  saw 
several  patients  in  whom  the  disease  affected  the  trachea  chiefly,  producing 
great  difficulty  of  breathing,  and,  in  one  case,  a  suppression  of  the  voice, 
and  I  heard  of  another  in  which  the  disease,  by  the  falling  of  the  trachea. 


EPIDEMICS  OF  INFLUENZA  725 

produced  a  cyanche  trachealis.  In  most  of  the  cases  which  terminated 
fatally,  the  patients  died  of  pneumonia  notha. 

"The  stomach  was  sometimes  aflFected  by  nausea  and  vomiting;  but 
this  was  far  from  being  a  universal  symptom. 

"I  have  met  with  four  cases  in  which  the  whole  force  of  the  disease 
fell  upon  the  bowels,  and  went  oflf  in  a  diarrhoea;  but  in  general  the  bowels 
were  regular  or  costive. 

"The  limbs  were  affected  with  such  acute  pains  as  to  be  mistaken 
for  the  rheumatism,  or  for  the  break-bone  fever  of  1780.  The  pains  were 
most  acute  in  the  back  and  thighs.  Profuse  sweats  appeared  in  many 
over  the  whole  body  in  the  beginning,  but  without  affording  any 
relief. 

"It  affected  adults  of  both  sexes  alike.  A  few  old  people  escaped  it. 
It  passed  by  children  under  eight  years  old  with  a  few  exceptions.  Out 
of  five  and  thirty  maniacs  in  the  Pennsylvania  hospital,  but  three  were 
affected  with  it.  No  profession  or  occupation  escaped  it.  The  smell  of 
tar  and  tobacco  did  not  preserve  the  persons  who  worked  in  them  from 
the  disease,  nor  did  the  use  of  tobacco,  in  snuff,  smoking  or  chewing, 
afford  a  security  against  it. 

"Even  previous  and  existing  diseases  did  not  protect  patients  from 
it.  It  insinuated  into  sick  chambers,  and  blended  itself  with  every  species 
of  chronic  complaint. 

"It  was  remarkable  that  persons  who  worked  in  the  open  air,  such  as 
sailors,  and  'long-shore-men,  (to  use  a  mercantile  epithet)  had  it  much  worse 
than  tradesmen  who  worked  within  doors.  A  body  of  surveyors,  in  the 
eastern  woods  of  Pennsylvania,  suffered  extremely  from  it.  Even  the 
vigour  of  constitution  which  is  imparted  by  the  savage  life  did  not  mitigate 
its  violence.  Mr.  Andrew  Ellicott,  the  geographer  of  the  United  States, 
informed  me  that  he  was  a  witness  of  its  affecting  the  Indians  in  the 
neighborhood  of  Niagara  with  p>eculiar  force.  The  cough  which  attended 
the  disease  was  so  new  and  so  irritating  a  complaint  among  them  that 
they  ascribed  it  to  witchcraft. 

"  It  proved  most  fatal  on  the  sea-shore  of  the  United  States. 

"Many  people  who  had  recovered,  were  affected  a  second  time  with 
all  the  symptoms  of  the  disease.  I  met  with  a  woman,  who  after 
recovering  from  it  in  Philadelphia,  took  it  a  second  time  in  New  York 
and  a  third  time  upon  her  return  to  Philadelphia. 

"Many  thousand  people  had  the  disease,  who  were  not  confined  to 
their  houses,  but  transacted  business  as  usual  out  of  doors.  A  perpetual 
coughing  was  heard  in  every  street  of  the  city.  Buying  and  selling  were 
rendered  tedious  by  the  coughing  of  the  farmer  and  the  citizen  who  met 


726  EPIDEMICS  OF  INFLUENZA 

in  the  market  places.  It  even  rendered  divine  service  scarcely  intelligible 
in  the  churches. 

"A  few  p>ersons  who  were  exposed  to  the  disease  escaped  it,  and 
some  had  it  so  lightly  as  scarcely  to  be  sensible  of  it.  Of  the  persons  who 
were  confined  to  their  houses  not  a  fourth  part  of  them  kept  in  their  beds. 

"  It  proved  fatal  (with  few  exceptions)  only  to  old  people,  and  to  F>ersons 
who  had  been  previously  debilitated  by  consumptive  habits.  It  likewise 
carried  oflF  several  hard  drinkers.  It  terminated  in  asthma  in  three  persons 
whose  cases  came  under  my  notice,  and  in  pulmonary  consumption,  in 
many  more.  I  met  with  an  instance  of  a  lady,  who  was  much  relieved  of  a 
chronic  complaint  of  her  liver;  and  I  heard  of  another  instance  of  a  clergy- 
man whose  general  health  was  much  improved  by  a  severe  attack  of  this 
disease. 

"  It  was  not  wholly  confined  to  the  human  species.  It  affected  two  cats, 
two  house  dogs  and  one  horse  within  the  sphere  of  my  observations. 

"In  the  treatment  of  the  influenza  I  was  governed  by  the  state  of  the 
system.  Where  inflammatory  diathesis  discovered  itself  by  a  full  or  tense 
pulse,  or  where  great  difficulty  of  breathing  occurred,  and  the  pulse  was 
low  and  weak  in  the  beginning  of  the  disease,  I  ordered  moderate  bleeding. 
In  a  few  cases  in  which  the  symptoms  of  pneumony  attended,  I  bled 
a  second  time  with  advantage.  In  all  these  instances  of  inflammatory 
aff'ection,  I  gave  the  usual  antiphlogistic  medicines.  I  found  that  vomits 
did  not  terminate  the  disease,  as  they  often  do  a  common  catarrh,  in  the 
course  of  the  day  or  a  few  hours. 

"The  duration  of  this  epidemic  in  our  city  was  about  six  weeks.  It 
spread  from  New  York  and  Philadelphia  in  all  directions,  and  in  the  course 
of  a  few  months,  pervaded  every  state  in  the  union.  It  was  carried  from  the 
United  States  to  several  of  the  West  India  Islands.  It  prevailed  in  the 
island  of  Grenada  in  the  month  of  November,  1789,  and  it  was  heard  of 
in  the  course  of  the  ensuing  winter  in  the  Spanish  settlements  in  South 
America. 

"The  following  winter  was  unusually  mild,  insomuch  that  the  naviga- 
tion of  the  Delaware  was  not  interrupted  during  the  whole  season,  only 
from  the  seventh  to  the  twenty-fourth  of  February.  The  weather  on  the 
third  and  fourth  of  March  was  very  cold,  and  on  the  eighth  and  ninth 
days  of  the  same  month,  the  mercury  stood  in  Fahrenheit's  thermometer 
at  4  degrees  at  seven  o'clock  in  the  morning.  On  the  tenth  and  eleventh, 
there  fell  a  deep  snow.  The  weather  during  the  remaining  part  of  the 
month  was  cold,  rainy  and  variable.  It  continued  to  be  variable  during 
the  month  of  April.  About  the  middle  of  the  month  there  fell  an  unusual 
quantity  of  rain.  The  showers  which  fell  on  the  night  of  the  seventeenth 


EPIDEMICS  OF  INFLUENZA  727 

will  long  be  connected  in  the  memories  of  the  citizens  of  Philadelphia, 
with  the  time  of  the  death  of  the  celebrated  Dr.  Franklin.  In  the  last 
week  of  the  month  the  influenza  made  its  appearance.  It  was  brought  to 
the  city  from  New  England  and  afi"ected,  in  its  course,  all  the  intermediate 
states.  Its  symptoms  were  nearly  the  same  as  they  were  in  the  preceding 
autumn,  but  in  many  people  it  put  on  some  new  appearances.  Several 
persons  who  were  afi'ected  by  it  had  symptoms  of  madness,  one  of  whom 
destroyed  himself  by  jumping  out  of  the  window.  Some  had  no  cough, 
but  very  acute  pains  in  the  back  and  head.  It  was  remarked  that  those 
who  had  the  disease  chiefly  in  the  breast  the  last  year,  complained  now 
chiefly  of  their  heads,  while  those  whose  heads  were  afi'ected  formerly, 
now  complained  chiefly  of  their  breasts.  In  many  it  put  on  the  type  of  an 
intermitting  fever.  Several  complained  of  constant  chills,  or  constant 
sweats;  and  some  were  much  alarmed  by  an  uncommon  blue  and  dark 
color  in  their  hands.  I  saw  one  case  of  ischuria,  another  of  an  acute  pain 
in  the  rectum,  a  third  of  anasarca,  and  a  fourth  of  a  palsy  in  the  tongue  and 
arms;  all  of  which  appeared  to  be  anomalous  symptoms  of  the  influenza. 
Sneezing,  and  pains  in  the  ears  and  frontal  sinus,  were  less  common  now 
than  they  were  in  the  fall;  but  a  pain  in  the  eye-balls  was  a  universal 
symptom.  Some  had  a  pain  in  the  one  eye  only,  and  a  few  had  sore  eyes,  and 
swellings  in  the  face.  In  two  persons  whom  I  saw,  the  cough  was  incessant 
for  three  days,  nor  could  it  be  composed  by  any  other  remedy  than  plentiful 
bleeding.  A  patient  of  Dr.  Samuel  Duffield  informed  me,  after  his  recovery, 
that  he  had  had  no  other  symptom  of  the  disease  than  an  efflorescence  on 
his  skin,  and  a  large  swelling  in  his  groin,  which  terminated  in  a  tedious 
abscess. 

"The  prisoners  in  the  jail  who  had  it  in  the  autumn,  escaped  it  this 
spring. 

"During  the  prevalence  of  this  disease,  I  saw  no  sign  of  any  other 
epidemic. 

"  It  declined  sensibly  about  the  first  week  in  June,  and  after  the  twelfth 
day  of  this  month  I  was  not  called  to  a  single  patient. 

"The  remedies  for  it  were  the  same  as  were  used  in  the  fall. 

"I  used  bleeding  in  several  cases  on  the  second,  third  and  fourth 
days  of  the  disease,  where  it  had  appeared  to  be  improper  in  its  first  stage. 
The  cases  which  required  bleeding  were  far  from  being  general.  I  saw  two 
instances  of  syncope  of  an  alarming  nature,  after  the  loss  of  ten  ounces  of 
blood;  and  I  heard  of  one  instance  of  a  boy  who  died  in  half  an  hour  after 
this  evacuation. 

"  I  remarked  that  purges  of  all  kinds  worked  more  violently  than  usual 
in  this  disease. 


728  EPIDEMICS  OF  INFLUENZA 

«r 

"The  convalescence  from  it  was  very  slow,  and  a  general  languor 
appeared  to  pervade  the  citizens  for  several  weeks  after  it  left  the 
city. 

"I  shall  conclude  this  account  of  the  influenza  by  the  following 
observations: 

"  I.  It  exists  independently  of  the  sensible  qualities  of  the  air,  and  in 
all  kinds  of  weather.  Dr.  Patrick  Russel  has  proved  the  plague  to  be 
equally  independent  of  the  influence  of  the  sensible  qualities  of  the 
atmosphere,  to  a  certain  degree. 

"2.  The  influenza  passes  with  the  greatest  rapidity  through  a  country, 
and  affects  the  greatest  number  of  people,  in  a  given  time,  of  any  disease 
in  the  world. 

"3.  It  appears  from  the  histories  of  it  which  are  upon  record,  that 
neither  climate,  nor  the  diff"erent  states  of  society,  have  produced  any 
material  change  in  the  disease.  This  will  appear  from  comparing  the  account 
I  have  given,  with  the  histories  of  it  which  have  lately  been  given  by 
Dr.  Grey,  Dr.  Hamilton,  Dr.  A.  Fothergill,  Mr.  Chisholm,  and  other 
modern  physicians.  It  appears  further,  that  even  time  itself  has  not 
been  able  materially  to  change  the  type  of  the  disease.  This  is  evident, 
from  comparing  modern  accounts  of  it  with  those  which  have  been 
handed  down  to  us  by  ancient  physicians. 

"I  have  hinted  in  a  former  essay  at  the  diminutives  of  certain 
diseases.  There  is  a  state  of  influenza,  which  is  less  violent  and  more 
local,  than  that  which  has  been  described.  It  generally  prevails  in  the 
winter  season.  It  seems  to  originate  from  a  morbid  matter,  generated  in 
crowded  and  heated  churches,  and  other  assemblies  of  the  people.  I  have 
seen  a  cold,  or  influenza,  frequently  universal  in  Philadelphia,  which  I 
have  distinctly  traced  to  this  source.  It  would  seem  as  if  the  same  sjjecies 
of  diseases  resembled  pictures,  and  that  while  some  of  them  partook  of 
the  deep  and  vivid  nature  of  mosaic  work,  others  appeared  like  the  feeble 
and  transient  impression  of  water  colours." 

A  third  epidemic  of  influenza  occurred  twenty-seven  years  after 
the  one  described  by  Rush.  We  have  a  brief  record  by  Daniel  Drake 
in  his  "Systematic  Treatise  on  the  Principal  Diseases  of  the  In- 
terior Valley  of  North  America."  This  work,  in  two  volumes  of 
nearly  a  thousand  pages  each,  was  published  after  his  death, 
and  is  a  monumental  record  of  the  history  of  clinical  medicine, 
as  he  and  his  colleagues  observed  it,  during  the  first  half  of  the 
last  century. 


EPIDEMICS  OF  INFLUENZA  799 

It  will  be  noticed  that  Drake  was  acting  as  an  army  surgeon  to 
two  regiments  of  militia  in  camps  when  the  influenza  swept  down 
from  the  East  to  the  frontier  post  in  the  Ohio  Valley  where  he  was 
stationed.  Drake  describes  it  in  these  words: 

"i.  History.  The  cause  of  this  malady  is  as  utterly  unknown,  as  the 
place  where  any  one  of  its  invasions  commenced.  I  am  unable  to  say 
how  often  it  has  traversed  our  Interior  Valley,  for  its  vast  uniformity  of 
surface  leads  to  an  extensive  production  of  the  endemic  disease  at  the 
same  time,  when  it  is  generally  called  influenza,  and  the  means  of  distin- 
guishing it  from  that  malady  do  not  exist.  It  is  sufficient  to  know  that 
we  have  been  invaded  by  this  exotic  epidemic. 

"The  first  and  greatest  invasion  of  this  kind  which  I  have  had  an 
opportunity  of  witnessing,  occurred  in  the  year  1807.  In  the  summer  or 
early  autumn,  the  newspapers  brought  the  intelligence  of  its  prevalence 
in  Europe  and  afterwards  that  it  had  reached  our  eastern  cities.  It  was 
in  October,  when  the  weather  was  fine  and  steady  that  it  appeared  in  this 
locality.  Two  regiments  of  militia  called  into  the  field  to  repel  from  our 
frontier  a  threatened  invasion  of  Indians,  were  at  the  time  encamped  a 
few  miles  out  of  town  and  I  was  then  in  attendance  upon  them.  These 
men  were  its  first  subjects,  the  people  of  the  town  still  being  healthy.  In 
a  few  days,  however,  it  reached  the  latter,  and  then  sought  out  the  scattered 
inhabitants  of  the  country.  At  that  time  there  was  but  little  communica- 
tion between  our  settlements,  yet  I  was  able  to  ascertain  that  it  'spread 
far  and  wide'  among  them. 

"I  need  not  give  the  history  of  any  other  prevalence,  as  this  illus- 
trates the  most  constant  of  the  laws  which  govern  influenza;  first  its 
progressive  extension  from  east  to  west;  second  Its  independence  of  all 
sensible  conditions  of  the  atmosphere;  third,  its  first  outbreak  in  bodies 
of  men,  and  compact  settlements. 

"2.  Symptoms.  While  the  symptoms  of  this  new  visitant  were  sub- 
stantially the  same  as  those  of  catarrh,  there  were  modifications  which 
deserved  notice.  Thus,  although  it  often  commenced  In  the  nares  alone, 
it  seemed  at  the  same  time  to  Invade  the  whole  respiratory  membrane. 
There  was  more  fever,  and  the  signs  of  Inflammatory  orgasm  were  often 
very  apparent;  but  the  highest  characteristic,  not  always  present,  was 
a  sense  of  sinking  and  prostration,  with  a  serious  feeling  of  disorder 
throughout  the  whole  system,  indicating  the  Impress  of  some  malig- 
nant agent.  In  subsequent  epidemics,  I  met  with  cases  of  the  same 
kind;  although  they  did  not  prove  fatal,  they  suggested  the  idea  of 
danger. " 


730  EPIDEMICS  OF  INFLUENZA 

Dr.  Drake  closes  his  account  by  noting  among  the  sequels  of 
influenza  the  occurrence  of  purulent  pleural  eff"usions  and  the  unusual 
number  of  cases  of  pulmonary  phthisis  that  developed.' 

» The  magnitude  of  the  recent  epidemic  of  influenza  has  not  been  fully  measured, 
but  it  seems  to  have  exceeded  any  previous  one  of  which  we  have  a  record.  The  London 
Times  has  stated  that  the  deaths  m  the  entire  world  have  numbered  twelve  millions.  We 
have  no  means  of  corrot>orating  this  estimate,  but  it  is  believed  that  the  deaths  in  the 
United  States  have  reached  over  500,000.  In  Canada  in  1918  there  were  13,880  deaths 
in  a  total  of  53,700  cases  of  influenza.  Late  reports  give  the  mortality  in  India  alone  at 
three  millions. 


VOTUM    MEDICI 

UT   CONATA   MEA   SINE   RATIONE   LUCRANDI 

AUT   PERDENDI    PERFICIAM. 

UT   SERVIAM   SINE   EXSPECTATIONE 

GRATIAE   FAMAEVE. 
UT   lUVEM   MAGIS   QUAM   lUBEAM. 
UT   MAGIS   CIRCUMVENIAR   QUAM   CIRCUMVENIAM 

FIDEIQUE   DESIM. 

UT   ONUS   OFFICI    SUSCIPIAM   POTIUS,    ET   MUNERIBUS 

QUAE   AD   ME   ATQUE   AD   HOMINES   PERTINEANT 

MAXIME    PERFUNGAR   QUAM   MIHI    IPSI 

COMMODUM   MAGNUM    CAPIAM. 

UT   VIRES   ET   SCIENTIAM   AD   OPUS   EFFICIENDUM 

HABEAM   QUODCUNQUE   DI   MIHI   DENT. 

UT  NIL  QUERAR. 

UT   CONSTANS,    FIDELIS   AMANSQUE   SIM. 

UT   OMNIA   SORDIDA   ET   MALA   ODERIM   SINE 

ACERBITATE   ERGA   EUM   QUI    PECCET. 

UT    FATUM    INELUCTABILE   FORTITER   OPPETAM. 

UT   MINISTRATIONEM   SOLITUDINIS,    SILENTI    ET   DOLORIS 

MENTE   OBSTINATA   ACCIPIAM. 

UT   MODERATE,    PALAM,    TEMPERANTER  VIVAM 

HAEC   OMNIA   SINT   MIHI    VOTA   COTIDIANA. 

Bv  Bayard  Holmes,  M.D., 
Chicago,  III. 


731 


SIR  WILLIAM  OSLER  AND  THE  JOHNS  HOPKINS 

HOSPITAL 

HOW  SIR  WILLIAM  OSLER  PROMOTED  AND  FOSTERED  THE  ACTIVI- 
TIES OF  HIS  STUDENTS  AT  THE  JOHNS  HOPKINS  HOSPITAL, 
I 889-1 905 

By  Henry  M.  Hurd,  M.D.,  Baltimore,  Md. 

THE  Johns  Hopkins  Hospital  of  Baltimore  was  opened  in 
May,  1889.  Although  Dr.  Osier  was  appointed  Physician-in- 
Chief  in  1888,  he  did  not  remove  to  Baltimore  until  the  fol- 
lowing year.  The  opening  of  the  hospital  for  the  reception  of  patients 
had  been  much  delayed  because  of  the  expectation,  unfortunately  not 
realized,  that  the  Medical  School  of  the  Johns  Hopkins  University 
would  be  established  in  connection  with  it.  An  attempt  had  already 
been  made  to  arrange  courses  of  study  at  the  Johns  Hopkins 
University  to  prepare  students  to  enter  upon  the  study  of  medicine 
when  H.  Newell  Martin  was  appointed  Professor  of  Biology,  and 
later  when  William  H.  Welch  became  Professor  of  Pathology  in 
1886.  After  spending  a  year  abroad  in  special  study.  Dr.  Welch 
took  up  his  residence  in  Baltimore  in  1887.  Laboratory  accommo- 
dations were  thereupon  provided  for  him  in  the  Pathological  Build- 
ing of  the  Johns  Hopkins  Hospital,  and  the  teaching  of  students 
began  there  in  1888.  Here  he  formed  classes  and  guided  the  work 
of  special  students,  inaugurating  laboratory  instruction  which 
proved  of  great  value,  not  alone  to  Baltimore,  but  to  the  country 
at  large,  when  the  newer  methods  of  bacteriology  and  pathology 
were  first  presented  to  medical  students.  At  the  opening  of  the 
Hospital  no  further  efi'ort  was  made  at  first  to  inaugurate  systematic 
instruction  in  medicine.  In  the  autumn  of  that  year,  however, 
largely  through  the  initiative  of  President  Oilman  of  the  Johns 
Hopkins  University,  who  had  co-operated  in  the  organization  of 
the  hospital,  courses  were  announced  and  classes  were  established 
for  post-graduate  students.  Such  classes  were  well  attended  and 

732 


SIR  WILLIAM  OSLER  AND  JOHNS  HOPKINS        733 

averaged  between  fifty  and  seventy-five  students  each  year  until 
the  establishment  of  the  Medical  School  in  1893.  They  served 
a  useful  purpose,  and  were  among  the  earliest  facilities  afforded  to 
students  in  the  United  States  to  become  familiar  with  bacteriology 
and  the  modern  methods  of  medical  investigation. 

Dr.  Osier  took  up  his  residence  at  the  hospital  during  the  first 
year,  and  was  surrounded  by  a  busy  company  of  young  medical 
men,  many  of  them  recent  graduates  in  medicine,  who  were  eagerly 
engaged  in  laboratory  work  or  medical  study  and  investigation. 

In  October,  1889,  through  the  hearty  co-operation  of  Doctors 
Welch,  Osier,  Halsted,  and  Kelly  a  Medical  Society  was  established 
which  has  continued  in  uninterrupted  operation  for  the  past  thirty 
years.  At  the  meetings  of  the  society  medical  and  surgical  cases  from 
the  hospital  or  dispensary  were  presented  and  terse  and  instruc- 
tive comments  were  made  upon  them.  Formal  papers  upon  new 
or  interesting  medical  topics,  followed  by  more  or  less  formal  dis- 
cussions, were  features  of  the  society.  The  moving  spirit  in  its 
organization  was  Dr.  Osier,  who  attended  its  meetings  with  great 
regularity,  and  engaged  actively  in  its  work.  The  meetings  were 
held  in  the  library  of  the  hospital,  and  were  attended  not  only 
by  members  of  the  staff"  and  post-graduate  students,  but  also  by 
representatives  of  the  medical  profession  in  Baltimore.  The  society 
soon  outgrew  the  limited  space  furnished  by  the  library  and  its 
sessions  were  later  transferred  to  the  medical  amphitheater.  At 
these  meetings  were  presented  the  results  of  original  studies  in 
malaria,  tuberculosis,  amebic  dysentery,  diphtheria,  typhoid  fever, 
neuro-histology,  and  various  branches  of  more  special  and  newer 
methods  of  laboratory  work.  Meetings  were  held  twice  monthly 
during  the  university  year,  and  proved  a  great  source  of  interest 
and  profit  to  the  students,  as  will  be  seen  by  the  reports  in  the 
Bulletin  of  the  hospital  and  the  papers  printed  in  detail  therein. 

Soon  after  at  Dr.  Osier's  suggestion,  a  Journal  Club  was  estab- 
lished, which  met  weekly  in  the  afternoon  or  evening,  and  furnished 
an  opportunity  for  all  who  were  interested  to  acquaint  themselves 
with  the  newest  medical  literature.  Internes  and  students  were 
appointed  to  present  summaries  of  the  current  literature  in  the 
various  branches  of  medicine.  Papers  were  read  sometimes  in 
extenso;  generally,  however,  summaries  were  presented.  The  eff"ect 


734       SIR  WILLIAM  OSLER  AND  JOHNS  HOPKINS 

upon  the  student  body  was  excellent,  and  all  students  were  thus 
stimulated  to  keep  themselves  in  touch  with  the  current  medical 
journals  of  America  and  Europe.  The  Journal  Club  soon  created 
an  appetite  for  medical  literature. 

In  the  following  year,  at  the  suggestion  of  Dr.  Osier,  the 
Historical  Club  was  established,  which  held  a  monthly  meeting, 
and  gave  an  opportunity  to  students  to  become  familiar  with  the 
history  of  medicine.  This  club  has  held  regular  meetings  during 
the  past  twenty-nine  years.  At  first,  a  series  of  formal  and  scholarly 
papers  was  presented  on  the  various  aspects  of  the  writings  of 
Hippocrates.  Later,  similar  papers  were  read  upon  the  writings 
of  Celsus  and  other  classical  writers.  Largely  through  the  initiative 
of  Dr.  Osier,  careful  sketches  were  given  of  the  earlier  physicians 
in  England  and  America.  The  list  of  Osier's  own  papers  is  a  long 
one,  and  includes  such  titles  as  "An  Alabama  Student, "  "  Influence 
of  Louis  on  American  Medicine,"  "John  Keats,  the  Apothecary 
Poet,"  "Oliver  Wendell  Holmes,"  "Thomas  Dover,  M.B.,  of 
Dover's  Powder,  Physician  and  Buccaneer,"  and  others.  The 
meetings  of  this  society  attracted  physicians  from  other  parts  of 
the  United  States,  and  many  interesting  papers  upon  historical 
topics  connected  with  medicine  were  thus  brought  before  the 
students:  and  many  of  them  were  published  in  the  Bulletin  of  the 
Johns  Hopkins  Hospital. 

Another  student  activity  which  Osier  initiated  was  the  Laennec 
Society,  for  the  study  of  tuberculosis.  This  grew  out  of  his  efi"ort 
to  familiarize  himself  with  the  extent  of  the  prevalence  of  tubercu- 
losis in  the  city  of  Baltimore.  At  his  own  expense  he  employed  two 
medical  students  to  follow  up  dispensary  cases  of  tuberculosis  at 
their  homes,  to  study  housing  conditions,  and  to  ascertain  and  to 
remedy  the  defects  existing  in  the  home  care  of  tuberculous  patients. 
The  condition  thus  brought  to  his  attention  by  the  efiforts  of  his 
students  proved  to  be  so  serious  as  to  decide  him  to  begin  a 
systematic  movement  in  the  community  towards  more  varied  and 
eflFective  work  for  the  detection  of  tuberculosis  and  its  relief.  He 
further  desired  to  place  a  knowledge  of  the  dread  disease  thoroughly 
before  the  public,  and  to  interest  physicians  generally  in  the  early 
detection  of  the  disease  and  its  prompt  treatment.  Hence,  the 
Laennec  Society  was  established,  and  held  regular  meetings  at  the 


SIR  WILLIAM  OSLER  AND  JOHNS  HOPKINS       735 

hospital  during  Dr.  OsIer*s  residence  in  Baltimore,  and  has  con- 
tinued them  since  his  departure  in  1905. 

It  is  of  special  interest  to  recall  the  fact  that  Dr.  Osier's  energetic 
and  enthusiastic  work  in  organizing  and  directing  the  Laennec 
Society  soon  came  to  the  knowledge  of  Mr.  Henry  Phipps  of  New 
York,  who,  unsoHcited,  placed  in  Dr.  Osier's  hands  a  liberal  fund 
for  the  fuller  prosecution  of  this  work.  The  out-patient  work  at 
the  Johns  Hopkins  Hospital  thus  made  possible  became  so  useful 
that  Mr.  Phipps  eventually  established  the  Phipps  Dispensary 
for  the  treatment  of  tuberculosis.  This  dispensary  was  inaugurated 
first  in  a  small  building  adjoining  the  General  Dispensary;  it  subse- 
quently was  much  enlarged  by  two  generous  contributions  from 
the  same  liberal  donor,  and  has  since  accomplished  a  remarkable 
work  in  the  detection,  diagnosis,  and  treatment  of  early  tuberculosis 
in  Baltimore  and  its  vicinity. 

All  of  these  societies  have  performed  an  important  work  in 
leading  many  medical  students  to  devote  themselves  to  medical 
research  and  investigation  in  every  department  of  medicine. 

In  conclusion  it  should  be  added  that  beyond  and  above  all 
other  influences  exercised  by  Dr.  Osier  was  the  daily  and  hourly 
spectacle  of  his  tireless  industry  as  a  teacher,  writer,  and  student 
of  medicine,  and  his  boundless  enthusiasm  over  the  rapid  progress 
of  medicine,  his  generous  recognition  of  the  efforts  of  others,  his 
unselfish  assistance  to  those  who  were  struggling  to  advance  it, 
and  his  unfeigned  pride  in  their  success.  During  the  whole  period 
of  his  residence  in  Baltimore  he  was  the  guide,  friend,  and  elder 
brother  of  his  students.  He  welcomed  them  to  his  hospitable  home 
and  regularly  gathered  them  in  larger  or  smaller  groups  to  read 
with  them  the  newer  literature,  to  discuss  the  problems  of  medicine, 
or  to  present  some  project  of  social  betterment.  He  gave  freely  of 
his  time  and  energies  to  all  who  came  under  his  notice,  and  ever 
had  an  open  hand  for  all  who  needed  aid.  His  presence  and  example 
were  a  benediction  to  all. 


AN  APPRECIATION  OF  HERMANN  WEBER 
By  A.  Jacobi,  M.D.,  New  York 

HERMANN  WEBER  was  a  lifelong  friend  of  mine.  I  knew 
him  first  at  Bonn  in  1849,  after  having  left  the  University  of 
Goettingen  in  1849.  My  sojourn  at  Bonn  lasted  from  my 
sixth  semester,  1849  to  1851,  where  after  my  eighth  semester  I  was 
graduated  in  medicine  in  April,  1851. 

Hermann  Weber  was  born  December  30,  1823,  of  a  German 
father  and  an  Italian  mother.  His  early  years  were  spent  in  country 
life  in  Bavaria  and  Hesse-Cassel,  and  he  studied  in  Fulda  until  he 
left  for  the  University  of  Marburg.  Here  he  met  Carlyle  during  his 
medical  studies.  From  Marburg  he  changed  to  Bonn,  where  his 
relations  with  Englishmen  were  still  more  frequent.  It  was  here  that 
Sir  Peregrine  Maitland,  Sir  Henry  Havelock,  and  Sir  James  Simp- 
son gained  an  influence  on  the  active  young  man.  It  was  through 
them  that  his  studies  of  Shakespeare,  and  of  English  in  general, 
became  more  matured  and  his  English  future  more  established. 

It  was  in  Bonn  that  he  graduated  in  medicine,  1848,  and  built 
the  foundation  for  his  future  greatness,  his  p)osition  there  being  that 
of  first  assistant  of  the  medical  clinic  of  the  university.  As  such, 
he  prepared  the  lectures  of  the  professor,  Friedrich  Nasse,  for  whom 
he  wfis  the  superintendent  of  the  medical  clinic.  In  that  capacity 
he  controlled  the  clinic-dispensary  work,  which,  under  Nasse,  was 
quite  extensive,  the  number  of  patients  from  the  poorer  classes 
treated  at  the  clinic  being  very  large,  consisting  of  adults  and 
children,  both  surgical  and  medical  cases.  All  the  advanced  students 
were  in  charge  of  patients,  in  great  part  respK)nsible  work.  The 
professor  himself  participated  in  the  active  work,  which  was 
guided  by  the  actual  assistants,  whose  activities  were  many.  The 
students  were  occupied  many  hours  every  day,  and  their  labors 
did  not  end  with  the  death  of  the  patients,  as  our  school  work  was 
not  closed  until  the  post-mortem  and  epicrises  were  finished. 

The  most  important  factor  in  my  labors  in  Bonn  was  the  method- 

736 


Hermann  Weber. 


AN  APPRECIATION  OF  HERMANN  WEBER       737 

ical  teaching  at  the  university.  There  was  but  one  instructor  in 
Germany  comparable  with  Nasse,  namely,  Krukenberg  of  Halle. 
Indeed  these  two  clinics  were  the  only  thorough  ones  in  German 
universities.  These  two  professors  were  actually  in  contact  with 
French  teaching.  We  students  were  fully  aware  of  what  was  going 
on  in  France  under  Laennec  and  Piorry,  and  were  quite  superior 
in  attainments  to  the  students  in  Vienna,  where  Skoda  taught  and 
Rokitansky  demonstrated. 

It  is  characteristic  in  the  hfe  of  Hermann  Weber  that  while  he 
continually  studied  and  learned,  he  never  ceased  to  teach.  I  early 
adopted  his  methods,  and  never  forgot  them.  I  learned  from  him  to 
combine  the  study  of  the  case  and  the  obligation  to  the  human 
creature  when  treating  a  patient,  and  I  applied  his  theories  in  later 
life  when  teaching.  My  connection  with  American  teaching  institu- 
tions was  of  the  same  nature,  both  scientifically  and  humanistically. 
I  have  been  assured  that  my  influence  as  a  general  teacher  has  been 
the  result  of  what  was  inculcated  by  my  lifelong  friend  and  teacher, 
Hermann  Weber.  There  should  be  more  such  friends  and  more 
such  teachers. 

His  first  public  position  in  England  was  that  of  house  physician 
in  the  German  Hospital  of  Dalston,  a  general  hospital  in  London, 
where  I  met  him  a  few  times  after  I  landed  in  England  as  a  refugee. 
Meanwhile  I  felt  that  our  paths  had  diverged  considerably.  He  had 
applied  for  admission  to  the  Royal  College  of  Physicians,  of  which, 
after  studying  in  Guy's  Hospital,  he  became  a  member  at  the  same 
time  as  Dr  William  Odiing,  in  1855.  About  that  time  he  joined  the 
"Medical  Society  of  Observation,"  which  attracted  all  the  younger 
men — his  co-workers — of  the  London  profession ;  and  from  that  time 
dated  his  friendship  with  Addison,  Edmund  Parkes,  Wilson  Fox, 
Hilton  Fagge.  It  was  in  1894  that  he  established  the  "  Weber-Parkes 
Prize"  for  the  study  of  tuberculosis,  which  has  been  awarded  five 
times  altogether. 

"Tuberculosis,"  "phthisis,"  "consumption"  were  his  lifelong 
topics  of  study  and  close  exertion.  The  British  profession  has  not 
failed  to  recognize  this.  On  the  Council  of  the  Royal  College  of 
Physicians  he  served  as  a  censor  in  1879  and  1880.  The  honor  of 
knighthood  came  to  him  in  1899.  He  became  a  consulting  physician 
to  the  Royal  National  Hospital  for  Consumptives  at  Ventnor;  to 


738       AN  APPRECIATION  OF  HERMANN  WEBER 

the  North  London  Consumption  Hospital;  and  to  the  King  Edward 
VII  Sanitarium.  He  was  connected  with  a  great  many  British  and 
foreign  learned  societies.  All  must  have  been  sources  of  intense 
satisfaction  to  him,  but  the  keenest  interests  of  the  warm-hearted 
man  were  his  lifelong  sympathies  with  poverty,  sickness,  and 
humanity. 

A  great  many  of  Weber's  publications  may  be  found  mentioned 
in  the  two  series  of  the  Index  Catalogue  of  the  Surgeon  General's 
Office,  Vols.  XVI  of  the  ist,  and  XXI  of  the  2d  series.  Extensive 
writings  of  his  form  part  of  Ziemssen's  Cyclopaedia  of  1880,  of 
Quain's  Dictionary, and  of  Allbutt  and  RoIIeston's  "System  of  Medi- 
cine." His  Croonian  lectures  before  the  Royal  College  of  Physicians 
in  1885  treated  extensively  of  phthisis,  like  others  of  his  special 
studies.  His  "Notes  on  the  Climate  of  the  Swiss  Alps"  (1864),  his 
"Treatment  of  Phthisis  by  Residence  in  Elevated  Regions,"  belong 
to  this  class. 

Many  results  of  his  studies  were  embodied  in  an  extensive  book 
published  with  his  son,  Dr.  F.  Parkes  Weber,  the  last  edition  of 
which,  "Climato-therapy  and  Balneo-therapy,"  appeared  in  1907. 

An  obituary  published  in  the  Lancet,  of  December  7,  19 18, 
speaks  of  him  in  warm  words.  The  claims  of  climatology  were  pub- 
licly recognized  owing  to  his  knowledge  of  the  subject,  Hermann 
Weber  being  an  ardent  mountain  climber  all  over  the  Alps  and 
Apennines.  His  recommendations  of  Switzerland,  Tyrol,  and  Italy, 
and  wintering  in  high  altitudes  were  generally  well  known.  His  ad- 
ventures in  the  Alpine  Club  were  matters  of  extensive  knowledge. 
In  his  sixty-eighth  year  he  climbed  the  Wetterhorn  and  the  Jung- 
frau;  in  his  seventy-third  year  he  still  made  extensive  Alpine  trips. 
He  did  not  give  them  up  until  he  reached  his  eightieth  year.  They 
made  him  the  great  judge  "amongst  half  a  dozen  of  British  prime 
ministers  and  a  number  of  members  of  the  royal  English  family." 
One  of  my  personal  letters  from  him,  which  was  burned  in  a  fire 
September  20,  19 18,  speaks  enthusiastically  of  his  tour  up  Mount 
Sinai  "a  few  years  previously." 

He  was  medical  officer  to  the  Central  office  of  the  North  British 
and  Mercantile  Insurance  Company  for  many  years;  was  president 
of  the  Life  Assurance  Medical  Officers'  Association  from-  1897  to 
1899;  and  his  presidential  address  on  heredity  in  relation  to  life 


AN  APPRECIATION  OF  HERMANN  WEBER       739 

assurance  showed  considerable  prevision  in  respect  to  matters  that 
have  since  become  subjects  of  more  elaborate  discussion  and 
arrangement. 

In  connection  with  his  extensive  active  and  scientific  studies, 
those  on  the  muscular  tissue  are  easily  appreciated. 

His  main  care  was  the  treatment  of  the  muscular  tissue.  In  his 
last  paper  ^  he  referred  to  much  of  what  he  had  taught  for  decades: 
The  principal  movements  ought  to  be  those  of  walking,  but  arms 
should  be  exercised  similarly,  not  only  of  the  young,  but  of  the  old, 
always  in  relation  to  the  different  ages  and  conditions.  Friar  Roger 
Bacon  knew  that  the  body  heat  decreased  after  the  age  of  forty. 

The  effects  of  the  muscular  actions  on  different  parts  of  the  body 
are  pointed  out,  as  follows: 

1.  Increased  afflux  of  blood  to  the  muscles  with  each  contraction. 

2.  Increased  nutrition  of  the  muscle  combined  with  improved 
metabolism  and  production  of  body  heat. 

3.  Increase  of  exchange  of  fluid  between  blood  and  tissues. 

4.  Facilitation  of  the  removal  of  waste  products. 

5.  Preservation  of  the  elasticity  of  the  thorax  and  lungs. 

6.  Abundant  supply  of  oxygen  for  the  blood  and  the  metabolism. 

7.  Maintenance  of  the  healthy  condition  of  the  organs  of  cir- 
culation, from  the  heart  to  the  smallest  arteries,  capillaries,  and 
lymphatics. 

8.  Massage  of  the  bones,  keeping  up  the  healthy  condition  of 
the  bone  substance  and  the  bone  marrow,  and  through  this  the 
formation  of  a  sufficiency  of  blood  efficient  for  the  fight  with  hostile 
bacteria  entering  it. 

9.  Increase  of  the  resisting  power  of  the  body  against  disease. 

10.  Persistence  of  the  working  capacity  of  the  brain  centers, 
which  initiate  the  action  of  the  different  sets  of  muscles. 

This  last  paper  of  his  is  characterized  by  assiduity,  like  every 
one  of  his  endeavors.  Even  when  he  participated  in  the  "Fest- 
schrift in  honor  of  A.  Jacobi,  M.D.,  LL.D.,"  1900,  p.  14,  in  his  "A 
Contagious  Form  of  Pneumonic  Fever  in  Children,"  he  displayed 
the  same  exactitude.  Even  in  his  last  article  he  extended  general 
knowledge  regarding  patients  oi  advanced  years. 

Hermann  Weber  died  November  11,  19 18. 

^  "On  the  Influence  of  Muscular  Exercise  on  Longevity,"  Brit.  M.  J.,  Feb.  23,  19 18. 


EDWARD  JENNER,  A  STUDENT  OF  MEDICINE,  AS 
ILLUSTRATED  IN  HIS  LETTERS 

By  Henry  Barton  Jacobs,  M.D.,  Baltimore 

THE  17th  of  May,  1919,  marks  the  170th  anniversary  of  the 
birthday  of  Edward  Jenner.  The  great  contribution  to  public 
health  and  happiness  which  this  man  made  has  not  only 
stood  the  challenges  and  criticisms  of  time  and  men,  but  stands 
to-day  as  the  most  momentous  of  all  prophylactic  measures  against 
disease  which  has  yet  been  suggested.  The  magnitude  of  his  one 
great  contribution  so  completely  engrosses  our  thoughts  of  Jenner, 
at  least  in  the  mind  of  the  present  generation,  that  all  other  ideas 
of  his  personality  or  of  his  work  are  quite  eclipsed,  and  so  it  has 
occurred  to  me  that  it  might  be  appropriate  in  this,  the  170th 
returning  year  of  his  birth,  to  recall  by  quotation  from  a  few  of  his 
own  letters  some  of  the  other  medical  subjects  which  engaged  his 
attention,  and  in  which  he  also  made  distinct  contributions  to 
medical  knowledge. 

Moreover,  the  fact  that  this  paper  is  one  of  many  others  offered 
as  a  token  of  esteem  and  affection  on  his  birth  anniversary  to 
another,  younger  by  just  an  hundred  years,  and  whose  earliest 
medical  contribution  also  related  to  smallpox,  seems  further  to  make 
the  subject  appropriate. 

i^H  Space  and  opportunity  together  compel  but  a  limited  number 
of  quotations  from  those  letters  at  hand.  It  is  believed  that  some, 
at  least,  have  never  before  been  published,  and  to  that  extent  are  of 
particular  interest. 

Care  has  been  taken  to  avoid  as  far  as  possible  quotations 
relating  to  the  discovery  of  vaccination.  For  the  sake  of  simplicity 
the  letters  are  arranged  in  chronological  sequence. 

In  reading  these  extracts  the  state  of  medicine  in.  Jenner's  time 
must  be  constantly  borne  in  mind.  He  lived  in  the  early  period  of 
the  great  medical  awakening  at  the  end  of  the  eighteenth  and  the 
beginning  of  the  nineteenth  century.  In  Britain,  Huxham,  CuIIen, 
the  two  Hunters,  Heberden,  Fothergill,  Lettsom,  Baillie,  Parry; 

740 


EDWARD  JENNER,  A  STUDENT  OF  MEDICINE      741 

in  France,  Corvisart,  Pinel,  Bayle,  Bichat,  Andral,  Laennec,  Louis, 
and  Piorey,  together  formed  a  group  from  which  modern  medicine 
has  its  origin. 

Jenner  fortunately  enjoyed  in  his  student  years  the  instruction, 
inspiration,  and  friendship  of  John  Hunter,  that  great  investigator 
and  seeker  after  Nature's  secrets.  To  him  he  owed,  largely  perhaps, 
his  love  for  the  study  of  natural  phenomena,  though  he  must  have 
possessed  an  innate  tendency  in  that  direction,  and  a  curiosity  to 
solve  problems  in  Nature  much  greater  than  that  which  moves 
most  young  men. 

The  following  letter  from  Hunter  to  Jenner  indicates  that  Jenner 
had  already,  at  an  early  date,  undertaken  investigations  of  his 
own,  and  had  become  interested  in  surgical  lesions  which  were  also 
of  interest  to  the  London  surgeon. 

Mr.  Hunter  to  E.  Jenner.^ 

Dear  Jenner:  I  received  your  account  of  your  experiments  on  the 
hedge-hog,  also  the  dog-fish,  for  which  I  thank  you.  I  have  now  received 
your  account  of  the  aneurismal  vein  with  the  cast,  and  showed  it  to  my 
pupils  this  evening  with  the  description. 

I  hope  you  will  be  able  to  procure  the  arm  when  the  man  dies.  If  you 
would  choose  to  have  it  published,  I  would  either  give  it  to  the  Medical 
Society  here,  or  send  it  to  Edinburgh  to  be  published  in  their  commen- 
taries. Let  me  know  your  inclination,  and  I  will  add  whatever  I  may  think 
wanting,  and  give  it  your  name.  I  am  very  happy  to  hear  that  some  of 
you  have  wished  to  communicate  your  ideas  to  another.  If  I  can  give  you 
any  assistance,  command  me;  I  shall  always  be  glad  to  hear  from  you  as 
an  individual,  or  as  from  the  Society.  Mrs.  H.  desires  her  compliments 
to  you.  Have  you  left  off  fossilizing? 

I  am,  dear  Jenner, 

Your  much  obliged  and  humble  servant, 

John  Hunter. 
London,  April  28th. 

In  May,  1777,  in  writing  to  Jenner,  John  Hunter  mentions 
his  own  indisposition,  with  which  he  had  suffered  from  time  to 
time  since  1773,  and  in  August  he  went  to  Bath  for  the  waters, 
where  Jenner  saw  him.  Jenner  at  once  concluded  that  Hunter's 

*■  Baron's  "Life  of  Edward  Jenner,"  I,  47. 


742      EDWARD  JENNER,  A  STUDENT  OF  MEDICINE 

trouble  was  due  to  the  angina  pectoris,  the  disease  from  which  he 
was  to  die  sixteen  years  later. 

So  much  impressed  was  Jenner  with  the  seriousness  of  Hunter's 
complaint  that  soon  after  he  wrote  to  Heberden  as  follows: 

E.  JenneTf  to  Dr.  Heberden^  1778.^ 

Sir:  When  you  are  acquainted  with  my  motives,  I  presume  you  will 
pardon  the  liberty  I  take  in  addressing  you.  I  am  prompted  to  it  from  a 
knowledge  of  the  mutual  regard  that  subsists  between  you  and  my  worthy 
friend  Mr.  Hunter.  When  I  had  the  pleasure  of  seeing  him  at  Bath  last 
Autumn,  I  thought  he  was  affected  with  many  symptoms  of  the  Angina 
Pectoris.  The  dissections  (as  far  as  I  have  seen)  of  those  who  have  died  of 
it,  throw  but  little  light  upon  the  subject.  Though  in  the  course  of  my 
practice  I  have  seen  many  fall  victims  to  this  dreadful  disease,  yet  I  have 
only  had  two  opportunities  of  an  examination  after  death.  In  the  first  of 
these  I  have  found  no  material  disease  of  the  heart,  except  that  the  coronary 
artery  appeared  thickened. 

As  no  notice  had  been  taken  of  such  a  circumstance  by  anybody  who 
had  written  on  the  subject,  I  concluded  that  we  must  still  seek  for  other 
causes  as  productive  of  the  disease:  but  about  three  weeks  ago,  Mr.  Pay- 
therus,  a  surgeon  at  Ross,  in  Herefordshire,  desired  me  to  examine  with  him 
the  heart  of  a  person  who  had  died  of  the  Angina  Pectoris  a  few  days  before. 
Here  we  found  the  same  appearance  of  the  coronary  arteries  as  in  the  former 
case.  But  what  I  had  taken  to  be  an  ossification  of  the  vessel  itself,  Mr.  P. 
discovered  to  be  a  kind  of  firm  fleshy  tube,  formed  within  the  vessel,  with 
a  considerable  quantity  of  ossific  matter  dispersed  irregularly  through  it. 
This  tube  did  not  appear  to  have  any  vascular  connection  with  the  coats 
of  the  artery,  but  seemed  to  lie  merely  in  simple  contact  with  it. 

As  the  heart,  I  believe,  in  every  subject  that  has  died  of  the  Angina 
Pectoris,  has  been  found  extremely  loaded  with  fat,  and  as  these  vessels 
lie  quite  concealed  in  that  substance,  is  it  possible  this  appearance  may 
have  been  overlooked?  The  importance  of  the  coronary  arteries,  and  how 
much  the  heart  must  suffer  from  their  not  being  able  duly  to  perform  their 
functions  (we  cannot  be  surprised  at  the  painful  spasms)  is  a  subject  I 
need  not  enlarge  upon,  therefore  shall  only  just  remark  that  it  is  possible 
that  all  the  symptoms  may  arise  from  this  one  circumstance. 

As  I  frequently  write  to  Mr.  H.  I  have  been  some  time  in  hesitation 
respecting  the  propriety  of  communicating  the  matter  to  him,  and  should 
be  exceedingly  thankful  to  you,  Sir,  for  your  advice  upon  the  subject. 
Should  it  be  admitted  that  this  is  the  cause  of  the  disease,  I  fear  the  medical 

*  Baron's  "Life  of  Edward  Jenner,"  I,  39;  I,  47. 


EDWARD  JENNER,  A  STUDENT  OF  MEDICINE      743 

world  may  seek  in  vain  for  a  remedy,  and  I  am  fearful  (if  Mr.  H.  should 
admit  this  to  be  the  cause  of  the  disease)  that  it  may  deprive  him  of  the 
hopes  of  a  recovery.  .  ,  . 

Here,  then,  is  the  first  intimation  that  angina  pectoris,  described 
by  Heberden  in  his  "Commentaries  on  the  History  and  Cure  of 
Diseases,"  is  at  least  partially  dependent  upon  coronary  artery 
disease  for  its  occurrence. 

Heberden  had  found  only  "small  rudiments  of  ossification  in  the 
aorta"  in  the  one  case  he  had  examined  p>ost-mortem.  In  Osier's 
seventeen  post-mortems,  recorded  in  the  eighth  edition  of  his 
text  book,  thirteen  presented  coronary  artery  disease.  We  must 
conclude,  therefore,  that  this  is  the  predominating  lesion  in  angina 
pectoris,  and  to  Edward  Jenner's  careful  observations  must  be 
given  credit  for  its  discovery — a.  fact  which  modern  medical  historians 
admit. 

In  the  letter  following  one  finds  that  as  early  as  1790  Jenner  had 
become  interested  in  hydatid  disease,  particularly  of  the  kidneys, 
and  had  suggested  a  remedy.  Full  report  of  the  case,  as  made  before 
the  Gloucestershire  Medical  Society,  July  28,  1796,  is  to  be  found  in 
British  Medical  Journaly  May  23,  1896.  Jenner  thought  the  patient 
improved  under  use  of  turpentine,  and  it  was  administered  because 
the  general  opinion  seemed  to  be  that  hydatids  were  insects. 

Whether  or  not  Jenner  accepted  Hunter's  reasoning  that  the 
hydatid  was  an  animal  rather  than  an  insect  we  are  left  somewhat 
in  doubt.  We  know,  however,  this  was  but  the  beginning  of  his 
inquiries  into  the  nature  of  this  parasite,  as  letters  to  come  will  show. 

Mr.  Hunter  to  E.  Jenner} 

Dear  Jenner:  I  have  just  received  the  favour  of  yours.  I  have  just 
now  forgot  the  case  of  hydatids;  but  if  there  was  any  thing  that  struck  me, 
I  dare  say  it  was  laid  by.  They  are  frequently  in  the  kidneys,  but  I  should 
doubt  your  oil  of  turpentine  having  any  merit  in  bringing  them  away.  My 
reason  for  supposing  them  animals  is  because  they  move  after  they  have 
been  extracted.  I  have  taken  them  out  of  the  head  or  brain  of  a  sheep,  and 
they  have  contracted  in  different  parts  of  them  when  put  into  warm 
water.  I  should  be  glad  to  employ  you  if  I  knew  in  what;  but  if  any 
thing  comes  across  my  imagination,  I  will  think  of  you.  The  measly  pork 
are  hydatids. 

»  Baron's  "Life  of  Edward  Jenner,"  I,  39;  I,  47;  I,  98. 


744      EDWARD  JENNER,  A  STUDENT  OF  MEDICINE 

I  am  afraid  of  your  friend  Mrs.  L.  There  is  a  hard  tumour  that  almost 

fills  the  pelvis,  most  probably  the  uterus.  How  does  Mrs.  Jenner  do?  do 

you  bring  her  to  London?  What  family  have  you  got?  My  compliments^to 

Mrs.  Jenner,  and  believe  me  to  be,  dear  Sir, 

Your  most  obedient,  and 

Most  humble  servant, 

^        ,      „  ,  .  John  Hu>rrER. 

December  8th,  1790. 

The  next  letter  from  Sir  Everard  Home,  son-in-law,  executor, 

and  successor  of  John  Hunter,  is  interesting  as  confirming  in  Hunter's 

case  the  ideas  Jenner  had  formed  regarding  angina  pectoris.  Such  a 

complete  substantiation  of  his  diagnosis,  made  sixteen  years  before, 

must  have  been  gratifying,  though  in  the  loss  of  his  friend  he  was 

deeply  grieved. 

Sir  Everard  Home  to  Dr.  Jenner.* 

Leicester  Square,  February  i8th,  1794. 

My  dear  Sir:  I  have  sent  you  by  the  Major  the  numbers  due  to  you 
from  the  Royal  Society.  I  am  well  assured  that  you  were  sincerely  afflicted 
at  the  death  of  your  old  and  most  valuable  friend,  whose  death,  although 
we  all  looked  for  it,  was  more  sudden  than  could  have  been  imagined.  It 
is  singular  that  the  circumstance  you  mentioned  to  me,  and  was  always 
afraid  to  touch  upon  with  Mr.  Hunter,  should  have  been  a  particular 
part  of  his  own  complaints,  as  the  coronary  arteries  of  the  heart  were 
considerably  ossified. 

As  I  am  about  to  publish  a  life  of  Mr.  Hunter,  which  will  contain  both 
the  symptoms  of  the  disease,  and  the  dissection,  I  shall  not  say  more  about 
it  at  present;  it  will  be  prefixed  to  the  work  on  inflammation,  and  we  hope 
to  have  it  printed  at  the  end  of  next  month. 

I  cannot  say  that  I  have  met  with  the  ossification  of  these  arteries  so 
frequently  as  other  alterations  of  structure  in  the  heart,  but  this  case  is 
very  much  in  favour  of  your  theory.  .  .  . 

Throughout  his  life  Jenner  maintained  firmly  that  the  digestive 
organs,  particularly  the  stomach,  were  in  the  animal  economy  the 
main  source  of  good  or  ill  health.  Here  again  he  anticipates  many 
a  later  advocate. 

The  following  letter  puts  this  belief  in  picturesque  words.  It 
also  indicates  that  diseases  of  the  eyes,  "these  invaluable  organs," 
had  claimed  his  thoughts. 

*  Baron's  "Life  of  Edward  Jenner,"  I,  39;  I,  47;  I,  98;  I,  104. 


EDWARD  JENNER,  A  STUDENT  OF  MEDICINE      745 

Cheltenham,  Octob'  8th,  1797. 

Wm.  Peter  Lunell,  Esq.,' 

Bristol. 

My  dear  Friend:  .  .  .  The  hour  may  come  (I  do  not  despair  of  its 
arrival)  when  my  stomach,  where,  wielding  an  absolute  Sceptre,  sits  the 
grand  Monarque  of  the  Constitution,  may  undergo  some  spontaneous 
change,  which  may  meliorate  its  present  condition;  and  then  I  trust  you 
will  find  me  a  more  orderly  correspondent,  and  that  William  Shakespear 
may  furnish  me  with  a  better  motto  than  that  which  is  now,  alas,  too 
applicable  "To  morrow,  to  morrow  &  to  morrow."  .  .  .  And  pray  how 
are  your  Eyes? — My  little  lecture  on  this  subject  did  not  sufficiently  catch 
your  attention.  I  know  not  why;  for  the  preservation  of  this  invaluable 
organ  has  occupied  much  of  my  Time,  &  f>erhaps  the  most  intense  of  my 
Studies  have  been  devoted  to  it. 

Believe  me 

Y"  very  faithfully 

Edw.  Jenner. 

Osier  says,  in  his  article  on  acute  endocarditis,  that  **  Bouilland 
first  emphasized  the  association  of  simple  endocarditis  with  rheu- 
matic fever.  Before  him,  however,  the  association  had  been  noticed." 

Bouilland,  living  from  1796  to  1881,  published  his  researches  on 
articular  rheumatism  and  the  coincidence  of  pericarditis  and  endo- 
carditis with  this  disease  in  1836. 

The  letter  which  follows  shows  that  Jenner  already  had  written 
a  paper  on  this  subject  prior  to  1805.  As  a  matter  of  fact,  on  July  29, 
1789,  "Mr.  Jenner  favored  the  Society  with  Remarks  on  a  Disease 
of  the  Heart  following  Acute  Rheumatism,  illustrated  by  Dissec- 
tions." (Record  of  the  Gloucestershire  Medical  Society.) 

From  the  wording  of  the  letter  one  would  certainly  infer  that 
the  observations  on  the  relation  of  the  heart  to  rheumatism  were 
original  ones,  and  that  to  Jenner  therefore  belongs  the  credit  of 
first  noticing  this  relationship.  The  Fleece  Medical  Society  was 
another  name  for  the  Gloucestershire  Medical  Society,  as  it  met  in 
the  parlor  of  the  Fleece  Inn,  Rodborough,  Gloucestershire. 

'  From  Dr.  Jacobs'  collection. 


746      EDWARD  JENNER,  A  STUDENT  OF  MEDICINE 

Berkeley,  Jan^  loth,  1805. 
Dr.  Parry," 

Circus,  Bath. 
Dear  Parry:  ...  A  neighbour  of  mine  died  yesterday  from  a  disease  of 
the  Heart,  which  followed  two  or  three  severe  attacks  of  acute  Rheumatism. 
You  may  probably  remember  a  paper  of  mine  that  was  given  into  the 
Fleece  Med.  Socy.  on  this  subject.  This  &  my  other  Papers  are  in  your 
possession.  If  you  would  be  good  enough  to  convey  them  to  me,  I  should 
be  extremely  happy  in  regaining  them  particularly  that  I  now  allude  to, 
as  I  am  confident  many  a  life  is  lost  by  not  shielding  the  Heart  at  the  going 
oflF  of  acute  Rheumatism,  which  not  unfrequently  at  that  time  feels  a 
morbid  determination  of  blood.  .  .  . 

Yrs.  truly, 

E.  Jenner. 

The  next  letter  indicates  that  Jenner  formed  early  a  sane,  if 
perhaps  radical,  view  of  the  value  of  medicinal  baths. 

William  Lunell,  Esq.,'' 
Bristol. 
My  dear  Sir:  .  .  .  Now  my  good  sir,  what  shall  we  do?  I  am  almost 
tempted  to  say,  will  not  Miss  Wait  be  benefitted  by  a  change  of  scene,  at 
least  by  that  of  changing  the  air  of  Bristol — a  murky  City,  for  the  aether 
of  Cheltenham?  Our  Springs  too  might  prove  salubrious.  In  the  days  of 
old  you  know,  we  could  reckon  but  on  one,  now  we  boast  of  eleven.  Our 
Chalybeate  Spring  rivals  that  of  Tunbridge,  and  our  sulphurated  Spa,  the 
famous  water  of  the  North.  It  is  really  a  very  extraordinary  fact  that  all 
the  medicinal  waters  of  any  celebrity  in  the  Island  are  to  be  found  concen- 
trated in  this  little  spot,  Bath  excepted,  and  to  this  I  attach  no  more  value 
than  that  which  flows  from  my  Tea  Kettle.  .  .  . 
Believe  me. 

Truly  yours, 

Edward  Jenner. 
Cheltenham,  5th  Janf  1811. 

The  appreciation  of  the  value  of  comparative  anatomy  and 
pathology  may  have  come  to  Jenner  from  his  master,  John  Hunter; 
at  any  rate  he  was  a  believer  in  it,  as  he  testifies  in  the  two  fol- 
lowing letters,  written  only  a  day  apart  in  1813,  when  sixty-four 
years  old.  They  indicate  how  interested  he  still  was  in  the  hydatid 
disease,  and  how  well  his  enthusiasm  for  investigation  persisted. 

•  From  Dr.  Jacobs'  collection. 
» Ibid. 


EDWARD  JENNER,  A  STUDENT  OF  MEDICINE     747 

The  language  is  poetic,  but  evidently  the  author  here  confuses  the 
two  hepatic  diseases,  cirrhosis  and  hydatids.  However,  the  desire 
for  greater  knowledge  is  most  praiseworthy. 

The  letter  to  "My  dear  young  Friend"  is  such  a  beautiful  one 
that  it  is  quoted  in  full. 

I  would  have  it  noted  that  Jenner's  mind  here  is  surely  con- 
templating an  active  agency  as  the  source  of  infection  in  typhus. 
Reference  to  this  will  be  made  later  on. 

Berkeley,  March  14,  1813. 
Dr.  Morgan," 

Great  Russell  Street, 

London. 

My  dear  Friend:  ...  I  have  not  been  in  town  since  the  summer  of 
181 1,  nor  much  at  Cheltenham,  preferring,  whenever  I  am  permitted,  the 
enjoyment  of  my  Cottage  in  this,  my  native  Village.  But  don't  think  I 
spend  my  time  in  idleness.  My  pursuit  has  lately  been,  when  uninter- 
rupted by  Vaccination,  the  morbid  changes  in  the  Structure  of  the  Livers 
of  Brutes,  which  has  led  me  to  some  conclusions  respecting  the  same  changes 
in  the  human.  Tis  hard  methinks  that  the  poor  animal  that  is  content  with 
what  the  meadows  afford  for  his  daily  Bill  of  Fare  &  whose  Cellar  is  the 
Pond  or  the  Brook,  should  perish  from  the  same  diseases  as  the  Drunkard; 
but  so  it  is.  There  are  Plants  which  some  how  or  another  are  capable  of 
throwing  the  state  of  the  Liver  into  that  sort  of  confusion  which  calls 
Hydatids  into  existence.  These  do  not  continue  long  in  their  native  state, 
but  produce  a  great  variety  of  Tubera,  cartilaginous,  boney  masses,  &c. 
In  other  instances  the  disease  originates  in  the  biliary  Ducts  which  become 
astonishingly  enlarged  &  thickened  in  every  part  of  the  Liver  and  finally 
destroy  it  in  various  ways.  This  is  the  outline  of  my  research.  The  Hydatid 
I  can  call  into  existence  in  the  Rabbit  in  about  a  fortnight.  .  .  . 

Your  much  attach'd 

Edw:  Jenner. 

Berkeley,  March  15,  1813. 

My  dear  young  Friend:  Before  I  received  a  confirmation  of  your 
convalescence  under  your  own  hand  &  seal,  I  had  the  happiness  of  hearing 
of  it  thro'  one  of  your  relatives  here.  Be  assured  it  was  a  great  happiness: 

•  From  Dr.  Jacobs'  collection. 


748      EDWARD  JENNER,  A  STUDENT  OF  MEDICINE 

for  had  the  Monster  Typhus  stuck  one  of  his  venom'd  Fangs  so  deep  as  to 
have  wounded  you  mortally,  I  should  have  griev'd  exceedingly.  What  is 
this  Fellow — into  what  apartment  of  our  Mansions  does  he  first  break  in, 
and  how  does  he  perform  the  work  of  havock?  Let  this  form  one  of  the 
subjects  of  our  conversation  when  next  we  meet.  I  have  both  seen  and  felt 
enough  of  this  burglarious  Depredator  to  excite  a  wish  to  detect  him  in  his 
first  hiding  place  where  he  makes  his  entry  &  think  I  have  found  him  out. 
I  have  been  endeavoring  to  trace  him  by  means  of  my  old  auxiliary, 
analogy — but  no  more  of  this  now,  except  a  hint  respecting  the  oxymuriatic 
gas.  On  this  as  the  best  contrivance  to  stop  his  rambling  from  place  to 
place,  I  have  a  very  confidential  reliance.  Let  me  entreat  you  to  keep  a 
watchful  eye  over  yourself  for  some  time  to  come.  The  activity  of  your 
mind  may  outstrip  the  powers  of  your  Muscles  and  keep  up  a  state  of 
debility,  which  would  be  overcome  by  a  due  quantity  of  rest.  Your  Father's 
Letter  tells  me  how  imperiously  you  are  call'd  upon  to  attend  to  this.  I 
should  say  some  lounging  amusement  would  be  the  thing  for  you.  A  long 
journey  is  out  of  the  question,  otherwise,  I  should  say,  come  and  take  it 
here;  at  all  events  when  you  are  able  I  shall  hope  to  see  you.  I  hear  much 
of  Mrs.  Ibbetson's  beautiful  Discoverys  among  vegetables  with  her  micro- 
scope. Who  would  have  thought  that  the  Nettle  concealed  for  so  many 
ages  such  treasures  for  the  Naturalist.  Have  you  seen  its  spiral  apparatus 
for  darting  forward  its  sting  when  irritated  by  the  touch?  How  beautifully 
the  God  of  Nature  displays  to  us  his  great  and  grand  Museum.  Were  all 
the  doors  to  be  thrown  open  at  once,  our  senses  would  be  confused  &  on 
recovery  we  sh*|  be  satiated,  just  like  those  (comparing  small  things  with 
great)  who  exhibit  the  Gallerys  of  Napoleon. 

/  am  still  going  on  with  my  inquiries  into  the  causes  and  effects  of  tbe 
morbid  changes  oj  tbe  Liver  in  Brutes.  This  has  led  me  into  some  conclusions 
respecting  tbe  same  morbid  cbanges  in  tbe  structure  of  tbat  Viscus  in  tbe 
buman  body.  How  wonderful  tbat  tbe  poor  animal  whose  Larder  is  the 
Meadow  and  whose  Cellar  is  the  brook  should  perish  from  the  same 
diseases  as  the  Drunkard;  but  so  it  is.  There  are  plants  which  somehow  or 
another  are  capable  of  throwing  the  Liver  into  that  kind  of  confusion  which 
calls  Hydatids  into  existence.  These  vermin  do  not  continue  long  in  their 
natural  state,  but  produce  a  great  variety  of  Tubera  in  all  manner  of  shapes 
and  forms.  They  are  variously  organiz'd;  fleshy,  boney,  cartilaginous,  etc. 
In  other  instances  the  disease  originates  in  the  deranged  state  of  the  biliary 
Tubes,  from  one  extremity  of  the  Liver  to  the  other,  which  become  as- 
tonishingly enlarged  in  their  diameter,  &  thickened.  Hence  such  havoc 
arises  that  Hydrops  Pectoris  is  the  consequence,  emaciation  &  death. 
Accept  this  as  just  an  outline  of  my  research,  which  from  a  thousand  inter- 


EDWARD  JENNER,  A  STUDENT  OF  MEDICINE      749 

ruptions,  and  I  must  confess  from  a  dislike  to  application,  has  been  con- 
ducted in  a  very  desultory  way. 

Pray  let  me  hear  soon  how  you  are  going  on,  &  thank  your  Father  for 
his  letter. 

Believe  me,  my  dear  Henry,  very  truly 

Yours, 

« T  T  /->         o  Edw.  Jenner. 

?  Henry  Cline.' 

It  may  be  recalled  that  Mrs.  Jenner  for  the  greater  part  of  her 
married  life  was  an  invalid,  suffering  from  a  chronic  pulmonary 
complaint,  with  an  occasional  hemorrhage;  that  Dr.  Jenner's  eldest 
son  died  of  consumption,  following  the  death,  from  the  same  disease, 
of  his  young  tutor,  who  had  lived  in  the  house.  It  is  no  surprise, 
therefore,  that  Jenner  should  have  been  extremely  anxious  about 
his  younger  and  only  remaining  son.  The  three  following  extracts 
relate  to  this  boy's  health.  They  show  a  keen  appreciation  of  the 
early  symptoms  of  pulmonary  tuberculosis,  the  insidious  nature  of 
its  onset,  and  the  value  of  fresh  air  in  its  treatment — differing  only 
from  the  modern  teaching  in  believing  that  its  temperature  should 
be  regulated. 

Cheltenham,  Dec'  2,  1813. 
Mr.  R.  Jenner,^" 

Henley,  Oxon. 

My  dear  Robert:  . . .  We  should  have  been  extremely  happy  to  have 
heard  by  him  that  you  were  looking  well  but  we  were  griev'd  to  hear  that 
you  look'd  pale  &  thin.  When  you  left  us  you  were  stout  &  in  good  health. 
Pray  tell  me,  are  you  entirely  free  from  Cough,  or  Complaints  about  your 
chest  of  any  sort  or  kind?  Such  as  a  sense  of  tightness  or  difficult  breathing 
or  using  any  great  exertion?  Have  you  at  any  time  a  pain  in  your  side 
under  the  Ribs?  Are  your  bowels  got  back  to  the  old  state  of  costiveness? 
Don't  fail  to  tell  me,  if  you  are  unwell  the  precise  feelings  you  experience. 

I  trust  you  diligently  attend  to  all  I  have  said  again  &  again  about 
cold. 

The  Post  is  going  out  &  I  can  only  add  with  what  anxiety  &  affection 
I  remain 

Truly  Yours, 

E.  J. 

•  From  Dr.  Jacobs'  collection. 
"  Ibid, 


750      EDWARD  JENNER,  A  STUDENT  OF  MEDICINE 

Mr.  R.  Jenner," 

Henley,  Oxon. 
Dear  Robert:  You  would  not  have  had  another  Letter  so  soon  had  It 
not  been  for  your  telling  me  that  your  Cough  still  continues.  In  my  opinion 
you  cannot  have  recourse  to  the  remedy  too  soon;  however,  at  all  events 
call  on  Dr.  Routh.  The  sort  of  Cough  you  had  when  here,  is  sometimes 
more  troublesome  to  cure,  &  is  apt  to  continue  longer  than  when  it  attacks 
at  once  with  greater  severity.  .  .  . 

Yr.  afFte.  Father 

E.  Jenner. 

Dec'  20,  1 813. 

Dr.  WORTHINGTON," 

Southend 

near  Upton. 
My  dear  Doctor:  .  .  .  My  poor  dear  Robert  came  home  from  School 
about  ten  days  since  with  a  bad  Cough  &  looking  so  peculiarly  ill,  so  like 
his  lost  Brother,  that  I  was  almost  struck  dead  at  his  appearance.  Thank 
God!  he  is  already  much  better  &  his  Cough  nearly  gone.  Our  sheet  anchor 
in  threatening  cases  I  believe  is  the  constant  breathing  of  air  duly  regulated 
as  to  temperature.  One  very  cheering  circumstance  is,  his  not  having  a 
quick  pulse. 

Most  truly  Your's 

Edw:  Jenner. 

The  next  letter  quoted  opens  up  fully  the  question  of  Jenner's 
conception  of  tubercle.  In  the  letters  describing  his  researches  upon 
hydatids  in  the  livers  of  brutes  he  speaks  of  "tubera"  being  formed, 
and  here  he  writes  of  another  "tubercle"  bursting.  It  is  probable 
that  the  words  relate  in  some  sense  to  pathological  processes, 
which,  to  Jenner,  seemed  more  or  less  identical,  though  we  are  not 
to  suppose  that  either  represents  the  true  tubercle  of  Laennec. 
That  there  must  have  been  some  kind  of  relation  between  the  tubera 
from  hydatids  and  the  tubercle  of  consumption  in  Jenner's  mind  is 
evident,  for  in  a  letter  to  the  Rev.  Dr.  Worthington,  of  December 
13,  1809,  quoted  in  Baron,  II,  407,  Jenner  says:  "What  dreadful 
strides  pulmonary  consumption  seems  to  be  making  over  every 
part  of  our  Island.  I  trust  some  advantage  may,  one  day  or  another, 
be  derived  from  my  having  demonstrably  made  out  that  what  is 
tubercle  in  the  lungs  has  been  hydatid." 

"  From  Dr.  Jacobs'  collection.  "  Ibid. 


EDWARD  JENNER,  A  STUDENT  OF  MEDICINE     751 

While  there  existed  this  unquestioned  confusion  in  Jenner*s 
conception  of  the  etiology  of  consumption,  I  cannot  but  believe 
that  he  had  a  glimmering  of  the  truth  that  consumption  was  de- 
pendent upon  the  introduction  into  the  lungs  of  some  active,  living 
substance,  and,  to  this  extent,  he  was  a  forerunner  in  thought  to 
all  those  who  since  have  demonstrated  the  exact  state  of  the  case. 
The  former  letter,  relating  to  typhus,  still  further  substantiates  my 
idea  that  he  was  searching  in  the  right  direction  in  his  efiFort  to 
explain  infection. 

It  may  be  well  to  remark  here  what  Hektoen  has  called  to 
attention,  namely,  that  in  Jenner's  "Inquiry,"  published  in  1798, 
he  gives,  in  the  words  of  Garrison,  "an  early  reference  and  a  clear 
explanation  of  anaphylaxis  or  allergy.  In  Case  IV,  he  notes  that 
inoculation  of  variolous  matter  in  a  woman  who  had  had  cowpox 
thirty-one  years  before,  produced  a  palish  red  efflorescence  of  the 
skin,  which  he  regards  as  almost  a  criterion  of  whether  the  infection 
will  be  received  or  not,  attributing  the  phenomenon  to  the  dynamic 
of  a  permanent  change  in  the  blood  during  hfe." 

Ch»  Murray,  Esq^"  Cheltenham,  Sept'.  22,  .8.4. 

Bedford  Row, 
London. 

My  dear  Sir:  After  the  accounts  you  must  lately  have  heard  from  this 
place  respecting  the  health  of  poor  Gen.  Lyman  you  will  not  be  surprised 
at  the  doleful  intelligence  I  now  communicate.  It  was  evident  yesterday 
that  he  was  in  a  dying  state,  &  this  afternoon  at  ten  minutes  past  one,  he 
expired  without  a  groan  or  a  struggle.  The  Miss  Lymans  bear  the  loss 
with  as  much  firmness  as  one  can  expect.  I  understand  the  family  in  Town 
will  be  appriz'd  of  the  event  by  this  Post. 

The  General's  state  of  health  continued  nearly  stationary  from  the 
time  of  his  arrival  here  till  the  commencement  of  the  late  warm  weather, 
soon  after  which  he  declined  rapidly  &  another  Tubercle  burst  about  a 
week  since,  which  discharged  profusely. 

Pray  make  my  best  Compt.  to  Mrs.  Murray  &  yr.  Family  &  believe 

me  very  truly  Your's  t,  , 

"^  Edw.  Jenner. 

In  the  letter  which  follows,  at  the  age  of  sixty-seven,  we  still 
find  him  interested  in  anatomy  and  evidently  engaged  in  some 
research  involving  the  lymphatics. 

"  From  Dr.  Jacobs'  collection. 


752      EDWARD  JENNER,  A  STUDENT  OF  MEDICINE 

Dr.  Burder," 

21  Southampton  Row, 

Russels  Square,  London. 

My  dear  Sir:  .  .  .  You  speak  of  your  engagements — I  hof)e  they  are 

of  a  nature  to  afford  you  pleasure  &  that  professional  calls  are  already 

occupying  part  of  your  time,  as  a  reward  for  your  attentions  &  laborious 

exercises  during  your  long  residence  in  Scotland.  I  could  wish  you  for  a 

moment  to  turn  to  your  Notes  on  the  Lymphatics,  &  just  tell  me  whether 

anything  new  is  said  of  their  structure — If  I  recollect  right  a  lymphatic 

has  two  Coats,  the  external  less  delicate  than  the  internal. 

Believe  me,  with  best  wishes,  dear  Sir 

Very  truly  yrs. 

D  t7  u     *L     o  /:  Edw.  Jenner. 

Berkeley,  Feb.  5th,  18 10. 

Here  are  Jenner's  views  regarding  wine  and  its  effects  upon  the 
human  system — a.  timely  subject  for  discussion  at  the  present  day. 

r»   T'   T  r    itK  Berkeley,  March  2,  18 16. 

R.  F.  Jenner,  Esq.,^* 

Exeter  College,  Oxford. 

My  dear  Robert:  Your  last  Letter  relieved   me   from   an   anxiety 

naturally  felt  respecting  your  health,  for  you  express'd  yourself  more 

vaguely  in  your  Letter  than  in  your  quotation,  as  in  the  former  nothing 

was  said  about  your  having  taken  a  Cold,  but  that  you  were  unwell;  so  I 

was  left  to  guess  at  the  nature  of  your  indisposition.  I  trust  you  have 

attended  to  my  suggestions  with  regard  to  the  Wine,  &  that  you  have 

only  sent  for  a  sufficiency  for  present  use.  You  will  be  coming  home  ere 

long  &  we  can  talk  more  about  the  poisonous  business  when  we  meet.  You 

know  my  fixt  &  unalterable  opinion  of  wine,  as  far  as  regards  its  deleterious 

effects  on  the  human  constitution.  .  .  . 

Yr.  affectionate  Father 

Edw^  Jenner. 

A  picturesque  letter  in  which  he  anticipates  animal  experimenta- 
tion in  physiology: 

Berkeley  31  August  18 16. 
Doctor  Charles  Parry,  M.D.^' 
Gay  Street,  Bath. 
My  dear  Charles:  . . .  with  regard  to  Pathology. 
The  impression  at  present  on  my  mind  is  that  somehow  or  another 
the  milk  of  the  mother  is  capable  of  receiving  impregnations  which  affect 
"  From  Dr.  Jacobs'  collection.  "  Ibid.  "  Ibid. 


EDWARD  JENNER,  A  STUDENT  OF  MEDICINE     753 

the  child.  We  have  not  yet  made  out  all  the  odd  things  going  forward  in 
the  animal  economy.  Tell  me  how  it  comes  to  pass  that  if  I  drink  a  glass 
of  good  cider  my  urine  smells  as  fragrant  as  the  bottle  when  just  uncorked? 
I  don't  give  this  as  a  parallel  case  but  as  a  puzzle.  There  must  be  a  short 
cut  from  the  stomach  to  the  Bladder.  Shall  we  ask  Riddle  about  these 
things?  What  if  we  were  to  fill  the  Stomach  of  a  Puppy  with  Mercury  first 
tying  up  the  Intestine  and  then  give  it  a  good  squeeze?  . . . 

Ever  yrs. 

my  dear  F-"^ 

Edw**  Jenner. 


This  interesting  letter  to  his  friend,  Dr.  Parry,  is  quoted  in  full 
as  the  finale  to  this  paper.  The  freshness  of  mind  and  spirit  is  de- 
lightful, despite  his  more  than  sixty-seven  years;  note,  too,  his 
wisdom  in  prescribing  diet  to  the  new-born  babe — anticipating 
completely  the  modern  modified  milk  treatment — and  again  recur- 
ring to  his  doctrine  that  the  stomach  is  the  key  to  health.  Note,  too, 
his  search  for  truth  and  his  rejection  of  terms  inexpressive  of  true 
processes,  his  realization  of  the  youthfulness  of  scientific  research, 
and  the  great  fields  which  yet  lay  ahead  for  investigation. 

*Tis  at  once  the  letter  of  the  young  enthusiast  and  the  resigned 
expression  of  one  who  realizes  fully  that  his  day  is  over,  and  is  con- 
tent to  await  the  future  whatever  it  may  bring — with  complete 
Aequinimitas. 

Chauntry  Cottage,  Berkeley,  Oct.  15,  18 16. 
Dr.  Charles  Parry," 

Gay  Street,  Bath. 
My  dear  Charles:  I  am  happy  in  writing  to  you,  &  making /or  me, 
rather  a  quick  reply  to  your  last  letter.  The  beauty  of  my  God-daughter 
must  be  secur'd  at  all  points  &  I  have  sent  her  the  enclos'd  little  present 
to  guard  her  from  the  spells  of  the  Fiend  that  takes  delight  in  spoiling 
Ladys  faces.  Mr.  Norman  had  better  use  the  points  on  the  arms  of  some 
Cottage  children,  and  having  produc'd  a  Pustule  (vesicle  if  it  must  be  so) 
to  vaccinate  from  that.  I  mention  this  because  the  Lymph  fresh  from  the 
arm  is  more  certain  than  when  inspissated,  even  (as  per  experiment)  tho* 
it  has  not  been  dried  five  minutes.  Emma  I  think  had  but  one  Pustule, 
which  I  fancy  went  thro*  its  course  undisturb'd — However,  it  w*^  do  the 
Lady  no  harm  to  test  her  from  her  sister's  arm.  The  matter  sent  is  fresh 
"  From  Dr.  Jacobs'  collection. 


754      EDWARD  JENNER,  A  STUDENT  OF  MEDICINE 

from  as  fine  a  Pustule,  as  ever  was  cali'd  up  by  Vaccine  Lancet.  Some 
Dolts,  Walker  of  Oxford  and  Shinlake  of  Taunton  have  lately  been  writing 
some  alarming  stuff  in  the  Yellow  Journal  declaring  thro*  thick  and  thin 
that  all  the  V.  matter  now  in  use  is  worn  out  by  being  work'd  so  long. 
Pretty  analogy  this — "the  world  is  young."  Now  the  fact  is,  that  this  par 
nobile  had  got  some  that  was  ruined  from  contamination  by  some  individual 
whose  skin  (from  disease)  was  incapable  of  producing  that  which  was 
correct.  This  sort  of  decompos'd  rubbish,  I  am  sorry  to  say,  gets  into  the 
hands  of  the  ignorant  and  produces  local  disgrace.  "The  world  is  in  its 
infancy." 

The  question  is,  respecting  the  stomach  in  the  nursery,  whether  that 
is  in  fault,  or  whether  Mrs.  Parrys  milk  is  in  a  state  fit  to  meet  its  powers 
of  digestion?  I  should  think  the  latter,  &  to  put  the  thing  to  issue,  I  w*| 
have  you  give  the  little  one  a  meal  or  two,  from  a  new  milk-pail.  The 
substitutes  for  milk  I  believe  are  all  bad.  The  best  deviation  I  have  found 
from  the  maternal  milk  is  that  of  the  ass — the  next  is  the  Cows  diluted 
with  one  third  part  of  water,  with  a  very  small  portion  of  sugar.  But  not 
unfrequently  the  process  of  Vaccination  acts  like  a  charm  in  correcting 
deviation  in  the  absorbent  system,  &  you  know  it  is  a  doctrine  in  my 
school,  that  the  Stomach  is  the  first — the  root,  the  foundation,  the  governor 
of  the  whole  family.  Away  with  the  term  Scrofula — Let  us  have  something 
expressive  of  morbid  action,  or  disease  of  the  Lymphatics.  You  know  how 
long  I  have  been  an  Hydatid-Hunter  &  tho'  Time  has  brought  me  to  a 
hobble,  yet  I  scramble  after  my  Game  as  hard  as  I  can.  And  what  do  you 
think?  I  seem  to  see  him  now  popping  out  of  a  Lymphatic,  A  speck,  or 
specks  (small  hydatids)  appear  where  a  like  portion  of  the  Lymphatic 
is  lost.  "The  world's  a  Baby." 

I  don't  take  in  the  Institution  Journal,  but  both  the  others.  I  must 
see  this  paper  on  the  Metals,  because  you  say  'tis  good.  How  goes  on 
Geology?  I  think  I  have  made  out  something  about  the  pebbles  in  our 
Basaltic-amygdaloid  Rock.  I  wish  you  would  look  at  your  Oolite  thro*  a 
good  magnifyer.  I  find — (stop — I  fancy  so)  they  are  made  up  of  con- 
centric layers;  the  first  crystaliz'd  on  a  small  atom,  a  fragment  of  stone. 
You  really  should  see,  with  a  geological  eye,  the  Country  around  this 
place — the  diversity  it  presents  would  delight  you,  and  if  my  good  old 
Friend  in  the  Circus  would  but  accompany  you,  then  after  a  day's 
hunt  we  w*!  sing  old  Rose  &  burn  the  Bellows.  I  really  want  to  sing  a 

swan-like  ditty  to  him  before 1  want  too,  to  write  to  him;  but 

when  I  think  of  setting  about  it  my  head  seems  so  full,  I  know  not  how, 
and  so  it  is   put  ofi"    until    to    morrow,    to    morrow    &    to    morrow. 


EDWARD  JENNER,  A  STUDENT  OF  MEDICINE     755 

"The  world's  a  Foetus."  Adieu  my  dear  Charles — Bob  &  Catherine  desire 
their  best  affections  with  myself  to  you,  Mrs.  Parry  &  the  accomplished 
Miss  Emma. 

Most  truly  yrs 

Edw*^.  Jenner. 
P.S. 

No  Cheltenham  for  me,  this 
winter. 


THE  INFLUENCE  OF  OSLER  ON  AMERICAN 
MEDICINE 

By  George  M.  Kober,  M.D.,  LL.D.,  Washington,  D.  C. 

DR.  OSLER  has  passed  his  seventieth  goal  post.  Sincere  per- 
sonal appreciation  of  the  master  work  of  this  chieftain  in  the 
art  and  science  of  medicine,  gratitude  for  the  kindly  inspira- 
tions experienced  through  his  influence,  and  the  sanguine  hope  that 
his  fair  example  may  stimulate  the  younger  generation  to  emulate 
his  noble  achievements  have  prompted  the  writer  to  lay  the  wreath 
of  tribute  at  the  feet  of  this  most  deserving  of  septuagenarians. 

Early  Life  and  Student  Days.  Sir  William  Osier  was  born  at 
Broad  Head,  Ontario,  July  12,  1849,  ^^^  son  of  F.  L.  Osier,  a  clergy- 
man of  the  Church  of  England.  His  were  not  only  rare  physical 
and  mental  characteristics  through  parental  inheritance,  but,  as 
told  him  by  his  old  and  true  friend,  Dr.  Jacobi,  at  the  farewell 
banquet  tendered  to  him  on  May  2,  1905,  "It  is  no  mean  felicity 
to  be  born  with  the  imprint  of  virtue." 

Those  familiar  with  the  portrait  of  Osier  as  a  schoolboy  at 
Trinity  College,  and  those  fortunate  enough  to  have  been  personally 
associated  with  him  in  later  years,  have  read  in  that  face  innate 
qualities  which  not  only  endeared  him  to  his  friends,  but,  in  the 
estimate  of  his  dear  old  mother,  "were  more  precious  than  all  his 
honors." 

Osier's  earliest  school  life  was  passed  in  the  school  of  his  native 
village,  following  which  he  went  to  Port  Hope  for  a  term  or  two  in 
Trinity  College  School  of  that  place,  and  later  still  he  entered 
Trinity  University  at  Toronto.  Devoted  to  his  books  during  hours 
of  class,  he  enjoyed  his  play  with  the  "playful  child  let  loose  from 
school."  Robust  of  health,  his  mind  matured  with  equal  pace. 

On  quitting  Trinity  College  young  Osier  entered  the  office  of 
Dr.  Bovell  at  Toronto  as  assistant,  and  there  he  inaugurated  his 
medical  studies,  later  matriculating  in  the  School  of  Medicine  of 
McGill  University,  Montreal,  graduating  in  1872. 

756 


INFLUENCE  OF  OSLER  ON  AMERICAN  MEDICINE    757 

We  learn  from  his  classmate,  Professor  F.  J.  Shepherd,  that 
while  a  conscientious  worker,  Osier  never  passed  for  "a  grinder." 
He  was  not  particularly  known  for  his  devotion  to  books,  nor  were 
his  efforts  entirely  focused  towards  success  in  examinations,  but  his 
main  attention  was  directed  towards  the  post-mortem  room  and  to 
all  hospital  work  within  reach.  He  was  beloved  because  of  his  social 
quahties,  kindliness  of  disposition,  and  characteristic  sense  of  hu- 
mor. Dr.  Shepherd  remarks: 

"While  he  did  not  graduate  very  high  in  his  class,  there  is  a  note  in 
the  convocation  that  a  special  prize  was  awarded  for  his  graduation 
thesis,  because  of  the  originality  it  displayed  and  the  research  it  evinced, 
and  because  of  the  collection  of  pathological  specimens  accompanying 
it  which  were  presented  to  the  museum.  In  the  light  of  his  after  studies,  it 
is  interesting  to  note  that  some  of  these  specimens,  still  in  the  college 
museum,  concerned  the  ulcers  of  typhoid  fever." 

As  a  student.  Osier  was  deeply  interested  in  comparative  pathology, 
and  as  teacher  in  subsequent  years  often  illustrated  a  point  in  human 
disease  by  a  reference  to  a  parallel  condition  in  the  lower  animals. 

How  carefully  he  prepared  himself  for  the  practice  of  medicine 
and  the  professor's  chair  is  evinced  in  the  fact  that  following  his 
graduation  he  spent  two  years  abroad  in  study  in  the  laboratory  of 
the  physiologist,  Burdon-Sanderson,  and  attending  the  clinics  of 
Jenner  and  Wilson  Fox,  Ringer  and  Bastian  in  medicine  and  the 
dermatological  clinics  of  Tilbury  Fox.  In  1873  he  took  the  degree 
of  licentiate  of  the  Royal  College  of  Physicians  in  London.  There- 
upon he  went  to  Berlin,  where  he  studied  pathology  under  Virchow, 
physiological  chemistry  under  Salkowsky,  and  clinical  medicine 
under  Frerichs  and  Traube.  In  the  early  part  of  1874  he  continued 
his  studies  in  Vienna  under  Bamberger,  Hebra,  and  other  noted 
clinicians. 

Teacher  at  McGill  University.  Upon  his  return  to  Montreal  in 
1874  he  was  appointed,  at  the  early  age  of  twenty-five,  professor 
of  the  institutes  of  medicine  at  the  McGill  University,  which  in- 
cluded the  course  of  physiology  and  a  series  of  twenty  lectures  on 
pathology.  In  1875-76  instruction  in  histology  and  demonstrations 
in  physiology  were  added  to  his  work,  and  the  following  year  a 
summer  course  in  pathological  histology.  Dr.  Osier  served  from 


758    INFLUENCE  OF  OSLER  ON  AMERICAN  MEDICINE 

1874-75  as  Physician  to  the  Smallpox  Hospital  of  Montreal,  and  it 
is  chronicled  that  he  sacrificed  his  salary  for  the  purchase  of  micro- 
scopes for  his  department  at  the  University.  Osier  himself  has  said 
that  a  man  should  come  into  internal  medicine  by  one  of  three  ways 
— physiological  chemistry,  physiology,  or  morbid  anatomy.  He  made 
himself  proficient  in  all  three  of  these  branches,  especially  in  pa- 
thology. 

In  the  winter  of  1875-76  his  autopsy  work  began  at  the  Mon- 
treal General  Hospital,  and  continued  for  eight  years  with  1000 
autopsies  to  his  credit.  In  1878  he  was  appointed  physician  to  this 
hospital,  and  there  began  his  career  as  a  brilliant  clinical  teacher. 
A  man  with  such  firm  scientific  foundations,  a  comprehensive 
knowledge  of  the  subject  presented  by  him,  and  his  personal  mag- 
netism, could  not  fail  to  command  the  respect  and  esteem  of  his 
students  and  professional  colleagues.  He  not  only  awakened  interest 
and  enthusiasm  in  modern  scientific  medicine  among  his  hearers, 
but  also  among  the  members  of  the  medical  societies.  Even  before 
the  completion  of  his  thirtieth  year  he  figured  as  a  leader,  and  his 
influence  was  felt  not  only  in  Canada  and  the  States,  but  merited 
for  him  later  the  appointment  of  Regius  professor  of  Oxford  Uni- 
versity. Osier's  recollections  of  his  early  teaching  career  are  charm- 
ingly and  modestly  set  forth  in  an  address  delivered  at  the  opening 
of  the  session  of  that  school,  September  21,  1899,  twenty-five  years 
after  the  faculty,  as  he  declared,  "with  some  hardihood  selected  a 
young  and  untried  man  to  deliver  lectures  in  the  Institutes  of 
Medicine." 

**My  first  appearance  before  the  class  filled  me  with  tremulous  uneasi- 
ness and  an  overwhelming  sense  of  embarrassment.  I  shall  not  forget  the 
nice  consideration  of  my  colleagues  and  the  friendly  greetings  of  the  boys, 
which  calmed  my  fluttering  heart.  One  permanent  impression  abides — 
the  awful  task  of  the  preparation  of  about  100  lectures.  After  the  ten  or 
twelve  with  which  I  started  had  been  exhausted,  I  was  on  the  treadmill 
for  the  remainder  of  the  session.  False  pride  forbade  the  reading  of  the 
excellent  lectures  of  my  predecessor,  Dr.  Drake,  which  with  his  wonted 
goodness  of  heart,  he  had  offered.  I  reached  January  in  an  exhausted  con- 
dition, but  relief  was  at  hand.  One  day  the  post  brought  a  brand  new  book 
on  physiology  by  a  well-known  German  professor,  and  it  was  remarkable 
with  what  rapidity  my  labors  of  the  last  half  of  the  session  were  lightened. 


INFLUENCE  OF  OSLER  ON  AMERICAN  MEDICINE    759 

An  extraordinary  improvement  in  the  lectures  was  noticed,  the  students 
benefited,  and  I  gained  rapidly  in  the  facility  with  which  I  could  quote 
the  translated  German.  Four  years  later  I  was  appointed  on  the  visiting 
staff  of  the  Montreal  General  Hospital.  What  better  fortune  could  a 
young  man  desire?  I  left  the  same  day  for  London  with  my  dear  old 
friend,  George  Ross,  and  the  happy  days  we  spent  together  working  at 
clinical  medicine  did  much  to  wean  me  from  my  first  love.  From  that  date  I 
paid  more  attention  to  pathology  and  practical  medicine  and  added  to  my 
courses,  one  in  morbid  anatomy,  another  in  pathological  histology,  and 
a  summer  class  in  clinical  medicine.  I  had  become  a  plurist  of  the  most 
abandoned  sort,  and  by  the  end  of  two  years  it  was  difficult  to  say  what 
I  did  profess,  and  I  felt  like  the  man  to  whom  Plato  applies  the  words 

of  the  poet: 

'Full  many  a  thing  he  knew 
But  knew  them  only  badly.* 

"Weakened  in  this  way,  I  could  not  resist  when  temptation  came 
from  pastures  new  in  the  fresh  and  narrower  field  of  clinical  medicine. 
After  ten  years  of  hard  work  I  left  Montreal  a  rich  man — rich  in  the 
treasures  of  friendship  and  good  fellowship,  and  those  treasures  of  widened 
experience  and  a  fuller  knowledge  of  men  and  manners  which  contact  with 
the  bright  minds  in  the  profession  necessarily  entails.  My  heart,  or  a 
good  bit  of  it  at  least,  has  stayed  with  these  treasures. " 

University  of  Pennsylvania.  In  the  summer  of  1884  Osier  received 
a  call  from  the  University  of  Pennsylvania.  When  the  invitation 
to  present  himself  as  a  candidate  for  the  position  of  professor  of 
clinical  medicine  at  Philadelphia  reached  him  at  Leipzig,  Dr.  Osier 
told  us  he  was  inclined  to  believe  it  a  joke.  Nor  was  he  disabused 
of  this  notion  until  two  weeks  later  a  cablegram  reached  him  to 
meet  Dr.  Weir  Mitchell  in  London.  He  added  with  his  characteristic 
humor,  "Boston  measures  men  by  brains,  it  is  said.  New  York  by 
*baw-bees,*  and  Philadelphia  by  breeding."  It  was  Mitchell's  task 
to  test  his  breeding.  He  did  so  by  having  him  eat  cherry  pie,  and 
noting  how  he  disposed  of  the  stones.  As  Osier  disposed  of  them 
discreetly,  the  breeding  question  was  settled. 

In  1884  Osier  was  elected  to  the  Fellowship  of  the  Royal  Col- 
lege of  Physicians  of  London,  and  in  1885  was  also  chosen  from 
the  newly  elected  fellows  of  the  College  to  deliver  the  "Gulstonian 
Lectures,"  a  singular  honor  which  he  most  efficiently  discharged, 
selecting  for  his  subject,  "Malignant  Endocarditis."  His  lectures 


76o    INFLUENCE  OF,  OSLER  ON  AMERICAN  MEDICINE 

were  based  on  his  studies  and  material  available  in  Montreal.  No 
wonder  that  a  man  so  highly  honored  by  the  Royal  College  had  been 
chosen  the  year  before  to  become  an  associate  of  Leidy,  Pepper, 
Stills,  and  other  leading  lights.  Osier's  advent  in  Philadelphia 
marked  a  turning  point  in  the  methods  of  teaching  medicine,  not 
only  in  Philadelphia,  but  in  the  States. 

In  Philadelphia,  as  in  Montreal,  as  was  well  said  by  his  friend, 
Dr.  James  G.  Wilson,  he  inspired  his  students  with  a  craving  for 
knowledge  based  upon  facts  of  the  ward,  of  the  microscope,  of  the 
laboratory,  of  the  post-mortem  room,  and  also  stimulated  their  in- 
terest in  medical  literature.  He  demonstrated  how  medicine  should 
be  learned  and  taught. 

He  also  insisted  with  the  younger  generation,  by  precept  and 
example,  that  it  is  not  necessary  for  every  physician  to  be  a  prac- 
titioner in  the  ordinary  sense,  but  that  long  years  of  hospital  and 
laboratory  work  constitute  a  better  equipment  for  the  teacher  and 
consultant. 

Johns  Hopkins  Medical  School.  In  1889,  at  the  age  of  forty, 
Osier  was  invited  to  Baltimore  to  take  charge  of  the  Medical 
Clinic  of  the  Johns  Hopkins  Hospital.  From  this  time  on  dates 
clearly  his  greatest  activity  and  usefulness  in  professional  work. 

Professor  William  H.  Welch  advises  us  that,  when  Dr.  Osier 
came  to  Baltimore,  the  main  intention  of  the  faculty  was  that 
the  hospital  should  form  an  integral  part  of  the  medical  school, 
and  that  opportunities  should  be  afforded  for  higher  clinical  train- 
ing. It  accordingly  seemed  expedient  that  students  should  be 
made  part  of  the  hospital  machinery,  and  to  Osier  is  due  the  credit 
of  working  out  the  details  of  the  scheme.  This,  indeed,  represents 
his  contribution  to  medical  teaching  in  America. 

Influence  on  Higher  Medical  Education.  Over  forty  published 
essays  and  addresses  bearing  upon  medical  education  and  medi- 
cal history  are  sufficient  warrant  of  Osier's  keen  interest  in  this 
subject. 

He  was  ever  a  staunch  advocate  of  higher  pre-medical  education 
requirements,  extension  of  the  period  of  professional  study  and  the 
substitution  of  laboratory  instruction  for  didactic  teaching.  In 
his  "Essay  on  the  Need  of  Radical  Reforms  in  the  Methods  of 
Teaching  Senior  Students"  he  advises  teachers  "to  give  to  students 


INFLUENCE  OF  OSLER  ON  AMERICAN  MEDICINE     761 

an  education  of  such  a  character  that  they  can  become  sensible 
practitioners." 

Dr.  Osier  was  convinced  that  it  is  the  duty  of  a  medical  school 
to  see  that  the  senior  student  "begins  his  studies  with  the  patient, 
continues  them  with  the  patient,  ends  them  with  the  patient, 
using  books  and  lectures  as  tools,  means  to  an  end. "  He  persistently 
maintained  that  the  ideal  hospital  is  one  connected  with  a  medical 
school,  with  the  professors  members  of  the  attending  staff.  In  this 
connection  he  writes: 

"The  work  of  an  institution  in  which  there  is  no  teaching  is  rarely 
first  class.  It  is,  I  think,  safe  to  say  that  in  a  hospital  with  students  in  the 
wards  the  patients  are  more  carefully  looked  after,  their  diseases  are  more 
fully  studied,  and  fewer  mistakes  are  made. " 

Osier's  methods  of  teaching  clinical  medicine  fitted  in  admirably 
with  the  general  policy  of  the  Faculty  that  the  students  should  be 
made  a  part  of  the  machinery  of  the  hospital.  As  a  result  the 
clinical  unit  was  maintained  in  the  fourth  year  as  taught  by  him, 
but  the  work  transferred  from  the  out-patient  department  to  the 
wards.  In  Osier's  judgment 

"  Each  man  should  be  allowed  to  serve  for  at  least  half  of  the  session 
in  the  medical  wards  and  half  in  the  surgical  wards.  He  should  be  assigned 
four  or  five  beds,  and  under  the  supervision  of  the  house  physician,  he 
does  all  the  work  in  connection  with  his  own  patients.  One  or  two  of  the 
clinical  units  are  taken  around  the  wards  three  or  four  times  a  week  by 
one  of  the  teachers  for  a  couple  of  hours,  the  cases  commented  upon,  the 
students  asked  questions,  and  the  group  made  familiar  with  the  progress 
of  the  cases.  In  this  way  the  student  gets  a  familiarity  with  disease,  a 
practical  knowledge  of  clinical  medicine,  and  a  practical  knowledge  of  how 
to  treat  disease. " 

Though  Dr.  Osier  disclaims  any  credit  for  his  teaching  method, 
it  is  nevertheless  unquestionable  that,  had  it  not  been  for  his  won- 
derful personality,  enthusiastic  and  effective  leadership,  American 
medical  education  might  still  be  fifty  years  in  arrears  of  that  of 
Europe.  It  required  a  man  of  his  broad  vision,  sound  judgment, 
a  devotee  to  his  profession,  and  a  statesman  in  medicine  to  make 
converts  to  the  cause  of  his  revolutionary  ideals. 


762    INFLUENCE  OF  OSLER  ON  AMERICAN  MEDICINE 

Dr.  Osier  has  always  felt  justly  proud  of  his  connection  with  the 
organization  of  the  medical  Clinic  of  the  Johns  Hopkins  Hospital 
and  the  introduction  of  the  old-fashioned  methods  of  practical 
instruction,  and  regards  this,  "as  by  far  the  most  useful  and  im- 
p>ortant  work  he  has  been  called  upon  to  do. "  We  who  are  familiar 
with  the  beneficent  effects  of  his  individual  influence  upon  his 
students  know  that  he  never  failed  to  do  his  best  work  and  to  keep 
far  afield  in  every  department  of  medicine,  but  over  and  above 
all  this  and  his  breadth  of  culture  and  broadminded  attitude 
towards  medical  problems,  he  possessed  attributes  which  are  rarely 
found  associated  in  any  other  single  individual. 

His  was  the  power  of  encouraging  and  inspiring,  of  firing  in  the 
youthful  heart  an  enthusiasm  for  a  chosen  life  work.  The  scenes 
enacted  with  his  students  in  the  out-patient  department  are 
fondly  recalled.  There  he  stood,  surrounded  by  his  boys,  lending 
them  friendly  advice  in  some  puzzling  case.  With  his  arms  thrown 
about  their  shoulders,  through  friendly  inquiry,  marked  with  oc- 
casional humorous  interspersions,  he  guided  them  on  to  a  satis- 
factory solution  of  every  difficult  problem.  Exact  always,  but  never 
dogmatic,  he  could  not  but  be  always  loved,  always  revered. 

We  feel  that  we  would  be  omitting  an  important  page  in  the 
story  of  Osier's  activities  were  we  to  pass  over  in  silence  those 
homely  Saturday  evening  gatherings,  held  at  the  table  round  in  his 
magnificent  library,  or  those  charming  essays  on  medical  history, 
which  Sudhofi"  estimated  "to  contain  more  of  the  historical  spirit 
than  many  learned  works  of  the  professional  historian." 

These  gatherings  also  enabled  him  to  familiarize  himself  with 
the  individuality  of  each  student,  and  in  his  charming  way  to  offer 
timely  and  valuable  suggestions  as  to  how  to  solve  certain  intel- 
lectual and  moral  problems.  Johns  Hopkins  Medical  School  has 
become  known  as  the  mother  of  medical  teachers,  and  since  213 
of  the  483  graduates  prior  to  1907  were  also  his  pupils,  are  or  have 
been  connected  with  our  medical  schools,  it  is  easy  to  infer  the  extent 
of  his  beneficent  influence. 

Dr.  Osier  realizing,  as  every  master  mind  necessarily  must,  the 
value  of  example,  ever  inculcated  on  his  student  body  esteem  for 
the  general  practitioner  and  old-style  country  doctor.  Most  of  his 
pupils  will  cherish  gratefully  the  words  addressed  to  them : 


INFLUENCE  OF  OSLER  ON  AMERICAN  MEDICINE     763 

"Many  of  you  have  been  influenced  in  your  choice  of  a  profession  by 
the  example  and  friendship  for  the  old  family  doctor  or  of  some  country 
practitioner  in  whom  you  have  recognized  the  highest  type  of  mankind, 
and  whose  unique  position  in  the  community  has  filled  you  with  laudable 
ambition.  You  will  do  well  to  make  such  a  man  your  example,  and  I  would 
urge  you  to  start  with  no  higher  ambition  than  to  join  the  noble 
band  of  general  practitioners.  They  form  the  very  sinews  of  the  profes- 
sion— generous-hearted  men,  with  well-balanced,  cool  heads,  not  scientific 
always,  but  learned  in  the  wisdom  of  the  sick  room,  if  not  in  the 
laboratories. " 

Osier  was  deeply  interested  in  the  progress  of  American  Medicine, 
and  proud  of  its  achievements,  as  shown  in  his  address  delivered 
at  the  opening  of  the  Museum  of  the  Medical  Graduates  College 
and  Polyclinic  in  London  on  July  4,  1900,  in  which  he  pointed  out 
the  silent  revolution  which  had  taken  place  in  medical  education, 
and  especially  in  the  cultivation  of  the  scientific  branches,  hospital 
equipment,  and  clinical  facilities. 

"The  most  hopeful  feature  is  a  restless  discontent  which,  let  us  hop>e, 
may  not  be  allayed  until  the  revolution  is  complete  in  all  respects.  Mean- 
time, to  students  who  wish  to  have  the  best  that  the  world  ofi"ers,  let  me 
suggest  that  the  lines  of  intellectual  progress  are  veering  strongly  to  the 
West,  and  I  predict  that  in  the  twentieth  century  the  young  English 
physician  will  find  his  keenest  inspiration  in  the  land  of  the  setting 
sun." 

It  is  quite  natural  that  a  man  with  such  high  hopes  and  aspira- 
tions would  strongly  resent  any  interference  with  the  legitimate 
and  humane  methods  employed  for  the  advancement  of  scientific 
medicine.  I  shall  never  forget  the  expression  of  scorn  in  his  eyes  and 
the  words  with  which  he  rebuked  the  enemies  of  scientific  progress, 
who  had  been  heard  before  the  U.  S.  Senate  Committee  on  a  bill 
for  the  further  prevention  of  cruelty  to  animals. 

"The  blood  just  surged  in  my  veins,  sir,  when  I  heard  two  men  address 
you  to-day  who  said  things  which  they  should  have  been  ashamed  to  say 
of  the  medical  profession,  of  men  who  daily  give  their  lives  for  their  fellows. 
.  .  .  With  reference  to  men  who  train  with  these  enemies  of  the  pro- 
fession, I  say  this,  that  I  scorn  them  from  my  heart."' 

*  See  "Hearing  on  Vivisection,"  February  21,  1900,  Government  Printing  Office, 
Washington.  The  Bill  failed  in  the  Committee  and  no  serious  attempt  has  been  made 
to  enact  what  Osier  characterized  as  "  a  piece  of  unnecessary  legislation. " 


764    INFLUENCE  OF  OSLER  ON  AMERICAN  MEDICINE 

Influence  on  the  Profession  at  Large.  The  many  invitations 
extended  and  accepted  by  Dr.  Osier  to  address  medical  societies 
attest  the  savory  widespread  influence  his  career  wielded  over  the 
medical  community  at  home  and  abroad.  His  text,  "Principles  and 
Practice  of  Medicine,**  graces  the  bookshelves  of  well-nigh  every 
English-speaking  physician  the  world  over. 

The  medical  societies,  the  efficient  vehicle,  as  he  took  it,  for  the 
dissemination  of  scholarship,  ever  received  his  heartiest  encourage- 
ment. Accordingly,  we  find  him  either  enrolled  as  an  active  member 
of  these  societies  or  fostering  their  foundation  because,  as  he  said 
to  the  members  and  friends  on  the  occasion  of  the  centennial 
celebration  of  the  New  Haven  Medical  Association,  January  6,  1903, 
"The  Society  is  a  school  in  which  the  scholars  teach  each  other, 
and  there  is  no  better  way  than  by  the  demonstration  of  the  more 
unusual  cases  that  happen  to  fall  in  your  way."  Through  these 
societies  he  awakened  interest  in  post-mortem  work,  the  presentation 
of  pathological  specimens,  and  in  library  equipment.  Through  them, 
also,  he  emphasized  what  a  well-equipped  and  properly  manned 
hospital  in  every  town  of  50,000  inhabitants  could  eff'ect  towards 
the  advancement  of  clinical  medicine.  Through  them  he  felt  that 
America  would  accomplish  more  for  clinical  medicine  in  five  years 
than  Germany  could  in  ten. 

Osier  was  one  of  the  most  active  founders  of  the  Association  of 
American  Physicians,  organized  at  a  meeting  held  in  the  office  of 
Dr.  Francis  Delafield,  New  York  City,  October  10,  1885.  Others 
present  at  this  time  were  Drs.  Wm.  H.  Draper,  Wm.  Pepper,  James 
Tyson,  George  L.  Peabody,  and  Robert  T.  Edes. 

The  first  scientific  meeting  of  the  Association  was  convened 
in  Washington,  June  17,  1886,  and  from  that  meeting  until  his 
departure  for  Oxford  he  was  recorded  absent  from  the  meetings 
but  twice.  Even  after  his  departure,  he  attended  several  meetings 
and  was  elected  an  honorary  member  in  19 12.  In  1894  he  was 
elected  President  of  the  Association,  and  in  his  address  delivered 
May  30,  1895,  he  spoke  in  part  as  follows: 

"At  the  opening  of  our  Tenth  Meeting  the  question  is  timely — How 
far  has  the  Association  fulfilled  the  object  it  had  in  view?  Have  our 
aspirations  and  hopes  of  1885  been  realized?  We  sought,  as  stated  in 
Article  I  of  our  Constitution,  the  advancement  of  scientific  and  practical 


INFLUENCE  OF  OSLER  ON  AMERICAN  MEDICINE    765 

medicine.  With  this  primary  object  we  sought  also,  as  Dr.  Delafield  said 
in  his  opening  remarks,  'An  Association  in  which  there  will  be  no  medical 
politics,  and  no  medical  ethics;  an  Association  in  which  no  one  will  care 
who  are  the  officers  and  who  are  not,  in  which  we  will  not  ask  from  which 
part  of  the  country  a  man  comes,  but  whether  he  had  done  good  work, 
and  will  do  more,  whether  he  has  anything  to  say  worth  saying  and  can 
say  it.'" 

Osier  believed  that  the  nine  volumes  of  the  Transactions  offered 
a  full  and  satisfactory  answer  to  the  first  question,  and  referred  to 
them  as  "the  repository  of  very  much  that  is  best  in  American 
medical  literature."  He  emphasized  the  widespread  and  effective 
interest  which  the  papers  of  Dr.  Fitz  on  Appendicitis  and  of  Dr. 
F.  M.  Draper  on  Pancreatic  Hemorrhage  had  produced,  and  suc- 
cinctly reviewed  some  of  the  topics  presented  for  discussion,  such 
as  typhoid  fever,  the  parasites  of  malaria,  tuberculosis,  diseases  of 
the  gastric  intestinal  tract,  diseases  of  the  heart,  blood,  blood  ves- 
sels, kidneys,  etc.  He  boldly  stated  that  several  papers  had  been 
presented  which  indicated  that  the  readers  had  failed  to  grasp  the 
scope  of  the  Association.  He  declared  that  the  Association  had 
already  shown  a  powerful  influence  on  the  study  of  pathological 
and  clinical  medicine  in  this  country,  that  there  was  at  present  an 
actual  scarcity  of  trained  pathologists  and  bacteriologists  and  a 
distinct  need  of  well-trained  special  clinical  physicians,  and  of  such 
physicians  and  of  pathologists  and  bacteriologists  should  the  Asso- 
ciation in  greater  part  be  composed. 

He  referred  to  the  limited  membership,  and  with  characteristic 
frankness  declared,  "We  should  all  understand  that  this  is  a  working 
society,  and  when  any  one  of  us  ceases  to  attend  regularly,  or  when 
our  interest  grows  lukewarm,  we  will  promote  best  the  common 
welfare  by  quickly  retiring."^ 

Osier  was  a  member  of  the  Council  of  the  Association  for  a 
number  of  years,  and  exercised  a  strict  but  just  censorship  over  the 
admission  of  members;  he  was  doubtless  the  most  active  worker 
in  that  body,  as  shown  by  ten  original  contributions  and  his  discus- 

'  The  membership  of  the  association  in  1886  was  limited  to  100,  which  was  increased 
in  1897  to  125,  in  1904  to  135  active  and  25  associate  members,  and  further  increased 
in  ipi2  to  160  active  and  25  associate  members.  Active  members  after  ten  years* 
service  may  be  transferred  to  the  list  of  emeritus  members.  Honorary  membership 
is  limited  to  25. 


766    INFLUENCE  OF  OSLER  ON  AMERICAN  MEDICINE 

sion  of  sixty-four  papers  presented  by  other  members.  He  was  as 
popular  as  a  teacher  among  his  colleagues  in  the  Association  as  with 
his  classes  in  the  medical  school.  The  young  and  the  old  were  at- 
tracted, inspired,  and  improved,  and  men  like  Jacobi  and  others 
much  older  than  he  had  told  him  that  they  were  glad  to  sit  at  his 
feet  and  listen  to  him.  Since  the  majority  of  these  men  were  occupy- 
ing professorial  chairs,  the  sphere  of  his  influence  has  been  greatly 
widened.  He  was  also  an  enthusiastic  founder  of  the  National  Asso- 
ciation for  the  Study  and  Prevention  of  Tuberculosis  in  1904,  and 
has  been  the  Honorary  Vice  President  ever  since  1905. 

When  Osier,  well-nigh  fifty  years  ago,  stood  upon  the  threshold 
of  his  professional  life,  he  stood  there  convinced  of  the  dignity  and 
responsibilities  of  his  lofty  vocation.  He  stood  there  convinced  that 
if  his  name  were  to  be  dug  deep  in  the  marble  walls  of  the  hall  of 
fame,  it  had  to  be  dug  therein  with  the  chisels  of  study,  honesty, 
and  truth.  He  has  now  lived  a  lifetime  of  life  and  lived  it  well.  He 
has  lived  a  lifetime  of  study,  as  evinced  by  over  240  contributions 
to  medical  literature.  He  has  lived  a  lifetime  of  service  to  his  fellow 
man,  to  which  bear  witness  his  contributions  to  preventive  medi- 
cine, his  active  participation  in  the  eradication  of  preventable 
disease,  his  kindly  ministrations  to  the  sick  poor.  He  has  lived  a 
lifetime  which  has  been  an  honor  to  his  profession  and  a  glory  to 
his  professional  brethren — a  lifetime  which  has  been  rewarded  with 
every  honor  and  trust  at  home  and  abroad  which  the  medical  com- 
munity could  possibly  bestow  upon  him.  He  has  lived  a  lifetime  of 
service,  and  during  this  lifetime  he  has  tempered  tenderness  with 
firmness,  condescension  with  authority.  His  only  protest  against 
cares  was  silence.  Dignity  met  his  responsibilities,  equanimity  his 
successes  and  griefs,  suff"erings  and  disappointments.  And  as  our 
congratulations  go  out  to  him  there  follows  the  sincere  hope  that  his 
days  of  activity  and  bliss  may  still  be  many  to  complement  this 
lifetime  that  shall  know  no  death. 


SERVETUS  NOTES 
By  Leonard  L.  Mackall,  New  York 

WRITERS  on  Servetus,  almost  without  exception,  seem  to 
be  pursued  by  some  singular  fatality  leading  to  bib- 
liographical inaccuracy — the  most  learned  become  il- 
logical, and  even  professional  bibliographers  Hke  van  der  Linde 
become  careless  for  the  occasion.  Hence  I  hope  that  the  following 
informal  notes,  ^  as  being  based  entirely  on  study  of  the  rare  original 
documents  and  accepting  nothing  on  mere  hearsay,  will  prove  of 
value  by  correcting  and  supplementing  various  statements  still 
current. 

The  Portrait  oj  Servetus.  There  is  much  uncertainty  about  por- 
traits of  Servetus.  Willis's  preface  states  expressly  that  the  portrait 
prefixed  to  his  book  was  concocted  by  the  author's  daughter,  yet 
it  was  selected  for  reproduction  by  Odhner,  19  lo.  Bernigeroth's 
engraving  in  Mosheim,  1748,  is  crude,  so  that  Sterling  ("Some 
Apostles  of  Physiology,"  1902),  Osier,'  and  Garrison  naturally 
preferred  Fritzsch's  frontispiece  in  Allwoerden's  "Historia,"  1728 
(not  1727,  cf.  Mosheim's  letter,  1728,  at  end  of  most  copies),  which 
is  re-engraved  anonymously  in  the  Dutch  version  of  1729.  AII- 
woerden  explains  (p.  i32f.): 

"Imago  haec  eius  satis  accurate  expressa  est  ex  antiquo  &  nitide  picto 
a  px^TViru),  quod  probabile  est  aliquera  ex  Serveti  amicis  fieri  curasse, 
cum  in  custodia  detineretur," 

and  that  the  original  painting  had  belonged  successively  to  Joh. 
Crellius,  Count  Schwerin,  Stenger,  Teuber  (Bishop  of  Halberstadt) 

'They  have  now  become  mere  notes  on  notes!  Though  written  solely  for  this 
volume  in  honor  of  Sir  William  Osier,  I  have  since  abridgecfthe  MS.  very  materially 
in  order  to  make  room  for  other  contributors.  However,  I  hope  to  print  it  later  in  full, 
perhaps  in  the  Annals  of  Medical  History;  and  hence  should  greatly  appreciate  any 
corrections  or  additions  for  such  future  use. 

*  Sir  William  Osier's  "Servetus,"  Oxford,  1009,  now  out  of  print,  but  reprinted  the 
same  year  in  the  Johns  Hopkins  Hospital  Bulletin  for  January,  1910;  also  translated 
into  German  in  the  Deutsche  Revue  for  December,  1909,  but  without  the  illustra- 
tions, which  had,  however,  been  retained  in  the  Bulletin,  and  reappear  in  Hemmeter's 
interesting  paper  in  Janus,  191 5,  from  the  original  blocks,  though  aifferently  combined. 

767 


768  SERVETUS  NOTES 

and  then  to  Peter  Ad.  Boysen  (author  of  the  "Historia  M.  Serveti," 
Wittenbergae,  1712)  who  lent  it  to  Mosheim.  Allwoerden  quotes  a 
long  letter  from  Boysen  on  the  subject.  That  painting  seems  now 
permanently  lost,  and  Fritzsch's  print  is  only  less  crude  than  that  of 
Bernigeroth.  But  Allwoerden,  who  had  perhaps  seen  the  original  as 
well  as  heard  about  it  from  Mosheim,  fortunately  gives  us  his  opin- 
ion of  the  previous  engravings  thus: 

"Ceterum  duplex  alia  Serveti  imago  nobis  occurit  aere  satis  eleganter 
expressa.  Altera  in  minori  folio  formae  circiter  octavse  descripta  erat: 
Sed  exempio,  quod  nobis  videre  licuit,  nee  chalcographi  nomen,  nee  aliud 
quid  adiectum  erat.  Alteram  vero  Christophorus  de  Sichem  in  patente 
charta  Amstelodami,  adiuncta  Serveti  historia  aut  potius  accusatione,  anno 
1607  expressit."  (p.  133,  of.  Mosheim,  p.  24if.) 

The  admirable  article  on  Servetus  in  the  new  Encyclopaedia 
Britannica  by  the  Rev.  Alex.  Gordon,  who  has  made  exhaustive 
researches  into  everything  connected  with  the  subject,  states:  "The 
only  likeness  of  Servetus  is  a  small  copperplate  by  C.  Sichem,  1607 
(often  reproduced),"  and  so  he  neatly  reproduced  this  small  head 
in  an  oval  as  frontispieces  in  his  privately  printed  "Personality  of 
Servetus"  (Manchester,  19 10,  cf.  the  crude  drawing  in  Cuthbertson, 
p.  52)  from  the  British  Museum  copy  of  the  "Grouwelen  der 
vornaemster  Hooft-Ketteren,"  Leyden,  1607.'  This  little  Dutch 
book,  consisting  of  short  notices  and  portraits  of  select  heretics,  was 
reprinted  several  times,  in  various  languages.  So  much  for  the  small 
head. 

The  UflFenbach-Tronchin  copy  of  the  larger  engraving  (extending 
to  the  waist)  examined  by  Allwoerden  (who  reprints  the  Dutch 
text  below  it)  and  Chauflfepie  (Nouv.  Diet.  Hist.  IV,  227,  cf.  Yair's 
English  translation  of  this  Life,  1771)  seems  to  have  disappeared 
entirely.  The  Geneva  Library  and  Tronchin's  family  know  nothing 
of  it.  But  the  British  Museum  and  I  have  the  "  Iconica  et  historica 

•  Some  copies  at  least  of  the  1607  "Grouwelen"  have  only  eight  portraits,  but  the 
Gennan  version  (Leyden,  1608)  has  seventeen,  and  so  has  the  Latin  "Apocalypsis 
insignium  aliquot  Haeresiarcharum "  by  "H.S.F.D.M.D."  (Leyden,  1608),  ancf  the 
very  similar  "Speculum  Anabaptisti  Furoris"  (Leyden,  1608).  The  English  translation 
by  John  Davies,  "Apocalypsis:  or  the  Revelation  of  certain  notorious  Advancers  of 
Heresie,"  was  first  issued  as  appended  to  the  second  edition  (1655)  of  the  "Pan- 
sebeia,  or,  a  View  of  all  Religions  of  the  World,"  by  that  polemical  ubique  Alex.  Ross 
(who  had  even  ventured  to  attack  the  Religio  Medici  in  his  "Medicus  Medicatus," 
1645).  Both  the  Dutch  and  English  versions  were  reprinted  several  times,  in  cruder 
form. 


Copper-plate  Engraving  of  Serveti's.  By  C  van  Sichem  (1607). 
From  Copy  in  the  Surgeon  General's  Library,  Washington 


SERVETUS  NOTES  769 

descriptio  praecipuorum  haeresiarcharum  per  C.  V.  S.  [i.e.,  Chris- 
tofFel  van  Sichem]  Arnheim,  1609,"  and  I  am  fortunately  able  to 
reproduce  here  an  impression*  with  German  text  in  the  Surgeon 
General's  Library,  van  Kaathoven  Collection  (cf.  Index  Cat.  Ill, 
289,  First  Series).  No  doubt  it  was  taken  from  the  "Historische 
Beschreibung  und  Abbildung  der  fiirnehmbsten  Haupt-Ketzer. 
Durch  C.V.S.A.  zu  Amsterdam,  bey  Niclauss,  Buchhandler,  1608." 
The  plate  itself  is  the  same  as  in  the  Latin  edition,  and  doubtless 
the  1607  Dutch  one  also  (cf.  Nagler  XVI,  346).  It  corresponds 
closely  to  Allwoerden's  frontispiece  and  evidently  the  small  head  of 
the  "Grouwelen,"  etc.,  was  merely  taken  out  of  this  careful  engrav- 
ing, which  is  thus  our  best  substitute  for  the  lost  original  painting 
from  which  it  was  made.  There  is  no  reason  why  we  should  not, 
with  Menendez  y  Pelayo  ("Hist,  de  los  Heterodoxos  Espanoles,** 
II,  312,  1880),  consider  this  portrait  as  at  least  "probablemente 
autentico." 

The  First  Two  Publications  of  Servetus.  The  genuine  original 
editions  of  the  153 1  and  1532  volumes  on  the  Trinity  (printed  by 
Johann  Setzer  in  Hagenau  near  Strassburg)  have  for  centuries 
been  so  extremely  rare  that  it  is  not  surprising  that  Osier,  Cuth- 
bertson,  and  Hemmeter  give  an  illustration  of  a  counterfeit  instead. 
Fortunately  I  own  the  genuine  Girardot  de  Prefond-MacCarthy- 
Bohn-Thorold  copy  of  both  bound  together  in  red  morocco,  bought 
by  the  elder  Quaritch  personally  at  the  Syston  Park  sale  in  1884. 
Nodier's  well-known  story,  **Le  Bibliomane"  (Paris,  ou  le  Livre 
des  Cent-et-un,  I,  183 1),  expressly  mentions  this  very  copy  as  sold 
in  the  MacCarthy  auction  (1817),  but  carelessly  assumes  its 
identity  with  the  Hoym-La  Valli^re  copy.  There  can  be  no  possible 
doubt  as  to  its  authenticity,  and  both  title-pages  are  now  repro- 
duced in  the  exact  size  of  the  originals. 

There  has  long  been  great  confusion  as  to  the  spurious  counter- 
feits of  these  two  books.  The  counterfeits  have  a  single  ordinary 
hyphen  in  the  words  TRINI-TATIS  and  DIALOGO-RUM  on  the 
titles,  instead  of  the  two  diagonals  of  the  originals  now  illustrated. 

*The  heading,  "Michael  Servetus,  ein  Spangiard,"  has  been  cut  from  the  upper 
margin.  Cf.  J.  K.  F.  Knaake — auction  cat.  Ill,  No.  975  (21-23  Febr.,  1907,  Osw. 
Weigel,  Leipzig)  and  Hiersemann's  cat.  346,  No.   1378. 

On  account  of  its  size,  the  text  ("Michael  Servetus  .  .  .  Gott  wolle  Richter 
sein."  24  lines)  and  ornamental  l>order  are  not  reproduced  in  the  present  volume, 
but  they  will  be  included  if  these  Notes  are  printed  in  full. 


770 


SERVETUS  NOTES 


DeBure's  Bibl.  Instr.  I,  1763,  is  the  only  direct  authority  for  any 
edition  of  either  book  with  two  horizontal  lines  instead  of  one,  and 

he  does  not  even  mention 
any  edition  with  only  one; 
so  that  it  is  quite  safe  to 
disregard  his  statement  as 
being  merely  inaccurate. 
There  seems  no  reason  to 
doubt  that  the  usual 
counterfeit  with  the  mis- 
print: CHHRSTUM,  on 
p.  8^b  (first  noted  by 
Ebert,  then  Graesse;  not 
mentioned  in  Brunet)  of 
the  153 1  book  was  made 
for  the  Rev.  Georg  Serpi- 
lius  (1668- 1 723),  a  promi- 


DE  TRINP 

TATIS     ERRORIBVS 
LIBRI     SBPTEM* 

^rMkhaeUm  Scrueto,4luls 
^eues  ah  Aragotti4 

hum  M.  D.  XXXr 

DIALOGO 


nent  clergyman  and 
learned  hymnologistof  Re- 
gensburg  (about  1721?). 
The  1532  book  was  evi- 
dently reprinted  at  the 
same  time.  The  printed 
catalogue  of  the  hbrary  of 
Serpilius  includes  copies 
of  **zweyeTley  editiones" 
of  both  these  books,  and 
also  of  the  very  rare  1607 
Roman  Index,  which  he 
likewise  counterfeited,^  ex- 
patiating on  its  rarity  in 
his  **S.  S.  Verzeichniiss 
einiger  Rarer  Biicher,"  I 
StiJck,  Frankfort  and 
Leipzig,  1723,  pp.  52-72.  This  is  certainly  very  significant,  and  we 
may  well  beHeve  that  he  gradually  sold  the  counterfeits  as  genuine 

•  Copies  of  the  Index  were  advertised  as  still  for  sale  in  the  G'dttingiscbe  Zeitungen  von 
gelebrten  Sacben  for  August  29,  1743,  p.  614. 


SLVli    DE   TRINITAXe 
UBRI    OVO. 


OS    IVSTICIA   REGKt    CHRI. 
fiifCapitttU  Qtuuuor* 

PER   MICHAELEM  SERVETO^ 
42b6  Keues ,  ab  Aragom 

Aim   M*  D.  XXXIf* 

^  Facsimile  of  title  pages  of  genuine  original  edi- 
tions of  the  first  two  publications  of  Servetus.  From 
the  Girardot  de  Prfefond-MacCarthy-Syston  Park 
copy,  now  in  the  possession  of  L.  L.  Mackall.  To  be 
carefully  distinguished  from  the  spurious  counter- 
feits. 


SERVETUS  NOTES  771 

(with  the  assistance  of  his  son),  especially  in  view  of  his  suspicious 
letter  dated  June  19,  1 721,  to  Seelen  (printed  in  the  latter's  "Selecta 
Litteraria,"  Lubecae,  1726,  p.  54)  stating  that  he  then  had  three 
copies  of  both  the  153 1  and  1532  volumes,  which  he  had  bought  in 
Poland,  where  he  could  still  get  more  but  at  a  high  price  !Cf.  Mosheim 
p.  309f.  But  in  behalf  of  Serpilius  I  can  state  at  least  that  he  owned 
also  the  "Religio  Medici,  Argent,  1665." 

Deschamps  and  G.  Brunet,  in  their  Supplement  to  J.  C.  Brunet's 
famous  "Manuel,"  assure  us  that  at  the  Morante  sale  (1872)  a 
copy  of  the  153 1  volume,  not  the  original,  was  in  its  original  binding, 
dated  1573,  and  that  there  was  a  similar  edition  of  the  1532  book, 
both  of  which  must,  therefore,  have  been  printed  much  earlier  than 
J.  C.  Brunet  intimated.  This  statement  has  hitherto  proved  a 
puzzle,  to  be  solved  only  by  reading  in  turn  the  various  passages 
involved;  and  this  could  not  be  done  conveniently. 

Thus  it  now  appears  that  Brunet  did  not  confirm  DeBure's 
inaccurate  statement,  or  intimate  that  there  was  anything  unusual 
about  the  MacCarthy  counterfeit.  Though  he  occasionally  refers 
to  Ebert,  he  never  mentions  the  misprint  CHHRSTUM  (cf.  above), 
which  may  have  been  present  in  both  the  MacCarthy  counterfeit 
and  the  problematical  Bearzi-Morante  copy.  The  Bearzi  and  the 
Spanish  Morante  catalogues  both  record  the  binding  of  this  copy 
as  old,  but  neither  mentions  any  date  on  it.  The  former  describes 
the  book  simply  as  a  "contrefacon"  (meaning  doubtless  the  usual 
one)  and  Morante  himself  states  positively  that  the  book  was  a 
reprint  made  in  Germany  about  the  middle  of  the  eighteenth  cen- 
tury. So  we  have  a  right  to  be  skeptical  as  to  the  authenticity  or 
significance  of  the  alleged  date,  1573,  in  this  case — especially  as  the 
same  authorities  seem  equally  sure  about  the  1532  book.  For  this 
very  Bearzi-Morante  copy  of  the  1532  volume  is  now  in  the  Hispanic 
Society  of  America,  and  on  examination  it  proves  to  be  merely  the 
usual  counterfeit,  such  as  is  so  often  bound  up  with  the  CHHRS- 
TUM reprint  of  the  1531  volume,  as  in  the  Bransby  (Sotheby, 
1828) — S.  M.  Jackson-Union  Theological  Seminary  (New  York), 
Jefferson  Medical  College  and  numerous  other  copies.  However, 
the  Hispanic  Society  owns  also  a  different  counterfeit^  of  the  same 

•  Both  these  Hispanic  Society  books  were  described  briefly  in  the  Knaake  auction 
catalogue  (III,  Nos.  971  and  972,  February,  1907)  and  then  in  Hiersemann's  catalogue 
346,  Nos.  1376  and  1377,  1907). 


772  SERVETUS  NOTES 

book,  and  this  one  has  not  only  a  flower  basket  and  no  cupid  in  the 
N  on  A2,  but  also  a  head  in  the  lower  half  of  the  P  on  C6b,  and 
further  (which  seems  not  to  have  been  noticed  hitherto),  the  title- 
page  reads  "IVSTITIA"  instead  of  "IVSTICIA,"  though  the 
latter  form  occurs  on  C6b  as  usual.  The  type  is  slightly  different, 
e.g.,  the  T  on  the  title-page,  and  the  paper  is  whiter  and  stronger. 
The  fly-leaves  bear  notes  in  German  referring  to  eighteenth-century 
books,  and  the  binding  (apparently  German  "Pappband")  seems 
to  belong  to  that  period  also.  Some  specialist  in  typography  might 
be  able  to  date  it  more  definitely.  The  ornamented  initials  on  A2 
and  C6b  are  in  both  reprints  of  this  book  wholly  different  from  those 
in  the  original  edition,  though  its  use  of  abbreviations  in  the  mar- 
ginal notes  is  copied.  The  CHHRSTUM  reprint  of  the  1531  vol- 
ume attempts  to  copy  the  initial  I  on  a2  but  prints  out  in  full  the 
original  abbreviations  in  the  marginal  notes.  Probably  there  are 
two  reprints  of  this  volume  also. 

The  1^46  Servetus  Manuscript  in  Paris.  It  is  universally  admitted 
that  the  earliest  printed  account  of  the  pulmonary  circulation  of  the 
blood  is  that  in  Servetus's  "  Christianismi  Restitutio,"  1553,  p. 
i69f.,  but  it  is  not  so  generally  known  that  the  passage  occurs 
already  in  the  1546  MS.  (corresponding  to  Christ.  Rest.  bks. 
III-VII  of  De  Trinitate  Div.)  bought  by  the  Bibliotheque  Nationale 
at  the  great  La  Valli^re  sale  in  1784  (lot  912,  for  240  livres).  It  had 
previously  belonged  (going  backward!)  to  Gaignat,  Hoym,  and  du 
Fay,  and  was  described  in  the  catalogues  of  their  libraries  as  well 
as  in  De  Bure's  "Bibliographic  Instructive"  I,  No.  757:1763  (cf. 
Allwoerden,  p.  191  f.,  and  Mosheim,  p.  458f.)  Chereau'  professed 
utter  ignorance  of  its  whereabouts,  though  it  had  been  listed  by 
Delisle,  and  Gordon  had  already  printed  a  careful  collation  in  the 
Theological  Review  for  July,  1878,  p.  4i7f.  This  MS.  is  not  in  the 
handwriting  of  Servetus,  but  it  is  a  copy  of  an  earlier  draft  of  the 

'  Chereau  strangely  says  {Bull,  de  VAcad.  de  Mid.  de  Paris,  1879,  P-  795):  "Nous 
ne  Savons  par  qui  il  a  6te  alors  (La  ValL,  sale  1784)  ach6t6,  ni  dans  quel  cabinet  il  est 
pass^.  Tollin  assure  Favoir  vu  .  .  .  nous  I'avons,  nous,  cherch6  en  vain" — 
but  the  MS.  had  been  duly  included  in  Delisle's  standard  official  Inventory  as:  "MS. 
Latin  18212.  Mich,  Servet,  de  Trinitate,  XVI  s.  [i^Ie].— La  Vall."  (Bibl.  de  I'ficole  des 
Chartes,  XXXI,  546,  1871,  for  1870).  Previously  it  was  known  as  MS.  "Fonds  La 
Vail.  162,"  as  cited  by  ToIIin  in  Vircbow's  Arcbiv,  1885,  CI,  59,  from  old  notes.  Months 
ago  I  ordered  a  photograph  of  the  circulation  passage  in  this  MS.,  but  war  conditions 
have  hitherto  delayed  it. 


SERVETUS  NOTES  773 

"Christianismi  Restitutio,"  corresponding  to  the  pages  in  MS. 
in  the  Edinburgh  copy  of  the  book. 

The  Paris  Copy  oj  the  "  Cbristianismi  Restitutio.*'  Much  has  been 
written  about  the  famous  Bibliotheque  Nationale  copy  of  the 
"Cbristianismi  Restitutio"  bearing  the  name  and  notes  of  CoIIadon, 
yet  its  history  is  still  partly  obscure.  It  has  suffered  from  both  fire 
and  moisture  in  the  opinion  of  A.  Laboulbene  (Revue  Scientifique, 
November  26,  1887),  whose  own  books  had  been  burned  a  few  years 
before,  so  that  he  knew  whereof  he  spoke. 

The  book  was  secured  at  the  La  Valli^re  sale  in  1764  (lot  913) 
for  412 1  livres,  due  to  the  insistence  of  the  Abbe  Desaulneys, 
Van  Praet's  predecessor  as  Keeper  of  Printed  Books. 

The  Due  de  La  Valli^re  had  acquired  this  book  at  the  Gaignat 
sale  in  1769  for  3800  livres,  Gaignat  bought  it  from  de  Cotte,  who 
got  it  from  the  de  Boze  collection  and  de  Boze  received  it  from  Dr. 
Richard  Mead,  in  whose  house  Chas.  Et.  Jordan  saw  it  in  1733. 
(Hist,  d'un  Voyage  Litt.,  La  Haye,  1735,  p.  i69f.)  Mead  still  had 
it  in  1740,  but  no  one  seems  to  have  noted  that  it  is  already  included 
in  de  Boze's  own  rare  quarto  catalogue,  1745. 

The  London  Reprint  of  the  "Cbristianismi  Restitutio,**  1725.  It  is 
usually  assumed  and  simply  stated  as  a  fact  that  the  unfinished 
London  reprint  (1723)  of  the  "Cbristianismi  Restitutio,"  was  made 
for  Mead  from  the  original  in  his  possession,  but  there  seems  to  be 
no  contemporary  authority  whatever  for  this  view,  or  any  proof 
that  he  owned  the  original  before  1733,  when  Jordan  saw  it.  Several 
years  ago  I  carefully  examined  such  documents  on  the  seizure  of 
the  reprint  as  could  be  found  in  the  London  Public  Record  Office, 
but  none  of  them  referred  to  Mead  even  indirectly. 

Mosheim  (p.  372f.),  who  was  greatly  interested  in  the  matter, 
beheved  that  the  actual  printing  was  done  by  George  Gallet  (who 
had  worked  for  the  Huguetans  in  Lyon,  and  then  was  active  as 
printer-publisher  in  Amsterdam)  for  Peter  Palmer.  I  agree  with 
Murr  that  Mead  probably  got  his  copies  of  both  original  and  re- 
print after  they  had  been  unexpectedly  seized  by  the  London 
authorities  on  May  29,  1723,  and  that,  just  before  sending  the 
original  to  de  Boze,  he  had  had  a  transcript  of  the  rest  appended 
to  his  copy  of  the  unfinished  reprint,  now  in  the  Bibliotheque 
Nationale. 


774  SERVETUS  NOTES 

The  Vienna  Copy  of  the  " Cbristianismi  Restitutio**  and  Murr*s 
Reprint  1790.  Of  the  Vienna  copies  of  the  original  and  of  Murr's 
reprint  only  a  word  can  be  said  here,  though  I  have  examined  them 
both  myself.  Perhaps  it  was  the  Prefect  of  the  Imperial  Library, 
Gottfried  Freiherr  von  Swieten  (the  musical  son  of  the  learned 
editor  of  Boerhaave),  who  induced  Count  Samuel  Teleki  von 
Szek  ( 1 739-1 822)  to  present  the  original  to  the  Emperor  Joseph 
II,  in  1786,  and  probably  he  had  already  tried  in  vain  to  buy  the 
La  Valli^re  copy  in  1784. 

Even  Menendez  y  Pelayo  and  the  Heredia  catalogue  (IV,  No. 
4106)  state  that  Murr's  reprint  was  made  in  1791,  but  the  very 
small  date  at  the  foot  of  the  last  page  of  text  reads:  1790,  and  this 
correct  date  is  twice  given  in  Murr's  own  "Adnotationes,"  etc. 
(1805,  pp.  29,  63). 

I  have  just  been  so  fortunate  as  to  discover  in  the  Harvard 
Library  ("C.   1346. 10.2*")  what  is  evidently  the  very  transcript 

*  In  fronte  huius  exempli  ad  dextram  subscriptum  legitur:  Danielis  Mdrkos 
Szent-Ivdnyi  Transylvano-Hungari.  Londini  i66i.  die  13  Maii.  Hocce  exemplum  idem 
est,  de  quo  Samuel  Crellius  in  limine  codicis  MS.  olim  Preussiani  meminit,  apud  loh. 
Laur.  Moshemium  in  hist.  lat.  Michaelis  Serveti,  pag.  204  [p.  181  of  usual  ed.],  et  in 
germanice  1748  pag.  344.     C.  T.  de  Murr."* 

used  by  Murr  for  his  reprint.  It  is  quarto  size,  bound  in  handsome 
German  calf  with  gilt  edges,  and  a  fly-leaf  bears  the  inscriptions: 
recto^  "Summa  Venerando  REINHARDO^  d.d.g.  de  Murr  d.  9 
Apr.  1808,"  and  versoy  "a.  1786  Biblioth.  Csesarese  illato*),  e  Vindo- 
bonensi  exempio,  typis  excuso  A.  1553,  in  8.  secundum  seriem 
paginarum,  exactissime  descriptus  est  hicce  liber  nitidissimus,  et 
editus  a  possessore  a.  1790  in  8  mai." 

•  "Reinhardo"  was  perhaps  Franz  Volkmar  Reinhard  (1753-1812),  a  learned  and 
influential  theologian  and  prolific  preacher  then  living  in  Dresden.  Like  the  original 
book  this  transcript  consists  of  734  pages  and  Errata;  but  there  are  usually  twenty-six 
or  twenty-seven  full  lines  to  a  page  (besides  the  running  title  and  catchword)  as  com- 
pared with  thirty-three  in  the  original,  and  thirty-six  in  the  reprint.  The  scribe,  who- 
ever he  was,  seems  to  have  done  his  work  very  carefully,  copying  even  the  misprints 
in  the  original,  and  using  similar  abbreviations,  which  are,  however,  expanded  in  the 
reprint.  Murr's  printed  list  of  Errata  reproduces  the  list  in  the  original  edition  without 
even  allowing  for  the  fact  that  the  number  of  lines  to  a  page  is  diflPerent.  There  is  one 
exception:  the  Harvard  MS.  reads  p.  3:  res  wm,  but  this  "omnium"  was  by  mistake 
omitted  in  printing,  and  so  this  correction  in  the  Errata  applies  to  the  reprint  only. 
The  anonymous  reviewer  in  the  Alls.  Lit.  Ztg.,  November  20,  1792,  noted  that  Murr's 
(p.  4,  I.  3):  verbo  cognationem  should  be  verbo  senerationem,  as  in  his  (?G6ttingen)  tran- 
script. The  Harvard  MS.  reads,  gHatioHe,  which  abbreviation  may  have  puzzled  the 
printer.^  The  MS.  agrees  with  the  reprint  in  reading  (p.  67,  I.  25)  apKij  for  apxv>  which 
the  reviewer  suggested  might  be  a  misprint  in  the  original. 

•The  words  "et  editus  ...  8  mai"  and  signature  were  evidently  written 
later  than  the  rest,  probably  at  the  same  time  with  the  presentation  inscription,  1808. 


SERVETUS  NOTES  775 

C.  G.  von  Murr,  who  Reprinted  the  "  Cbristianismi  Restitutio.** 
Christoph  Gottlieb  (Theophilus)  von  Murr  (1733-1811)  of  Nurem- 
berg was  one  of  the  last  survivors  of  the  now  extinct  species  Poly- 
bistor.  Of  very  varied  learning,  he  wrote  learnedly  on  every  imagin- 
able subject,  was  familiar  with  all  possible  languages,  and  cor- 
responded with  learned  men  in  many  countries,  including  England. 
He  translated  Fielding's  "Voyage  to  Lisbon"  into  German  (Altona, 
1764,  anon.)  and  Thos.  Pennant's  "British  Zoology"  into  Latin. 
His  elaborately  learned  "Adnotationes  ad  Bibliothecas  Hallerianas 
Botanicam,  Anatomicam,  Chirurgicam  et  Medicinae  Practicse  cum 
Variis  ad  Scripta  Michaelis  Serveti  Pertinentibus"  (Eriangen,  1805, 
4to)  contains  even  a  tabular  "Quadrupedum  Sinicorum  Dispositio, 
methodo  Linneanse  accomodata.  Auct.  C.  T.  de  Murr,"  printed  in 
Chinese  characters!!  But  it  must  be  added  that  his  knowledge  of 
medicine  was  learned  and  antiquarian  rather  than  practical;  he 
was  not  an  M.D.,  and  his  own  death  is  said  to  have  been  immedi- 
ately caused  by  his  clumsy  use  of  a  catheter  on  himself! 

The  writer  who  exerted  the  chief  influence  on  Murr  in  his  youth 
was  none  other  than  our  old  friend  Sir  Thomas  Browne!  "Praeter 
alios  paternse  bibhothecae  libros  maxime  arrisit  Murrio  nostro, 
tredecim  tum  annos  nato,  Tbomae  Broivnii  Pseudodoxia  Epidemica, 
quippe  quae  ipsius  animum  ita  afi"eceret,  ut  sibi  proponeret,  omne 
quod  rehquum  esset  vita  tempus  imp>endere  vero,"  the  preface  by 
Joh.  Ferd.  Roth  to  the  sale  catalogue  of  Murr's  books  (Nuremberg, 
181 1,  with  portrait)  tells  us,  and  its  No.  5036  is:  "Brown,  Th. 
Pseudodoxia  Epidemica,  d.i.  Von  den  Irrthiimern  des  gemeinen 
Mannes;  a.  d.  Engl.  u.  Lat.  durch  Christian  Peganium  (Knorr  von 
Rosenroth)  mit  Figg.  (Nbg.)  1680  Pd."  (sic\)  Murr  visited  London 
in  1757  and  again  in  1761-62,  and  thus  made  the  acquaintance  of 
Birch  (who  took  him  to  the  Royal  Society  and  the  Soc.  of  Anti- 
quaries), Hill,  Askew,  Taylor,  Parsons,  Wm.  Hunter,  Swinton, 
Glover,  Garrick,  Hogarth,  and  others,  with  several  of  whom  he  later 
corresponded. 

Murr  was  a  bibliophile,  and  he  was  particularly  interested  in  Ser- 
vetus.  In  1784  he  pubhshed  an  elaborate  bibliographical  essay  on  the 
"Christianismi  Restitutio"  in  his  Journal  Zur  Kunstgescbicbte  and  a 
"Gesch.  d.  ber.  span.  Arztes  Michael  Serveto,  in  welcher  Calvins 
schandliches  Verfahren  gegen  denselben  an  Tag  gelegt  wird.  Mit 


776  SERVETUS  NOTES 

Urkunden  und  einer  Kupfert.  gr.  80."  is  listed  among  Murr's  works, 
then  (1805)  "theils  unter  der  Presse,  theils  ...  in  Hs.  zum  Drucke 
bereit,"  but  it  was  apparently  never  printed.  Attention  was  called 
to  Murr's  Servetus  collection  in  the  second  edition  of  his  book  on 
Nuremberg,  and  the  titles  are  given  in  the  auction  catalogue  issued 
in  181 1  after  his  death. 

Murr's  chief  Servetus  treasure  is  No.  5102,  in  the  Catalogus: 
"Magistri  Guidonis  de  Cauliaco  Inventarium  s.  CoIIectorium  partis 
chirurgicalis  Medicinse  s.  Chirurgia.  Lugd.  1537.  Ldr.  Titulus  manii 
restitutus.  Hoc  ex.  ob  Mich.  Serveti  manum  quae  ad  calcem  libri 
conspicitur,  a  b.  Poss.  magni  aestimatum."  I  have  tried  in  vain  to 
trace  this  book. 

Unknoum  Works  by  Servetus.  The  unique  personal  item  just 
mentioned  leads  naturally  to  works  by  Servetus  hitherto  introuvable 
or  entirely  unknown.  Mosheim  at  first  categorically  denied  (1748, 
p.  73,  341)  but  later  (1750,  p.  34,  cf.  27,  after  d'Artigny  II,  103) 
admitted  the  existence  of  the  **  In  Leonardum  Fuchsium  Apologia. 
Autore  Michaele  Villnovano,  1536,"  though  he  had  noted  that 
J.  G.  Schenck's  "Biblia  latrica/*  1609,  p.  410,  had  given  the  title. 
HaIIer*s  "Bibl.  Med.  Pract."  II,  34,  starred  the  title,  thus  indicating 
that  he  himself  owned  a  copy,  but  Murr  ("Adnot."  p.  6of.)  made 
elaborate  efforts  to  trace  it  without  result.  Willis  (p.  103  n.)  found 
the  title  in  the  printed  catalogue  (III,  287  :  1870)  of  Dr.  Williams's 
Library,  London,  but  the  book  itself  could  not  then  be  found.  It 
has,  however,  since  then  turned  up  again.  Gordon  had  it  photo- 
graphed in  1909,  and  he  has  located  another  copy  elsewhere.  Mean- 
while ToIIin  had  discovered  extracts  from  it  in  Seb.  Montuus's 
"Dialexeon  Medicinalium,"  Lugd.  1537,  and  reprinted  them  in 
Rohlfs's  Deutscbes  Arcbv.  J.  Gescb.  d.  Medicin,  1884,  VII,  409f. 

Sudhoff  (whom  I  met  at  the  Leipzig  Book  Exhibition  in  19 14) 
kindly  informed  me  that  a  wholly  unknown  work:  "M.  Villanouanus, 
Epistolae.  Lutetiae  1536,"  had  recently  come  to  light  and  then  disap- 
peared again  in  the  stock  of  a  bookseller  in  Leipzig.  Let  us  hope 
that  he  will  find  it  and  turn  it  over  to  Sudhoff". 

Chronology  of  Servetus  on  the  Circulation  of  tbe  Blood.  The  fol- 
lowing notes  emphasize  the  chief  dates  in  connection  with  the  well- 
known  passage  on  the  Circulation  in  the  "Christianismi  Restitutio." 

1546.  Earliest  known  form  of  the  passage  on  the  circulation  by 


SERVETUS  NOTES  777 

S.  Represented  by  the  MS.,  not  in  handwriting  of  Servetus,  now  in 
the  Biblioth^que  Nationale,  Paris,  MS.  Lat.  182 12.  Variants  carefully 
printed  by  Alex.  Gordon  in  Theological  Review^  July,  1878,  p.  4i7f. 

1553.  " Christianismi  Restitutio,"  printed  by  Balthasar  ArnoIIet 
at  Vienne,  France.  1000  printed,  but  only  three  now  known,  Paris, 
Vienna,  and  Edinburgh  Univ.  (this  copy  lacks  first  16  pp.,  replaced 
by  transcript  from  the  original  draft).  Reprinted  1723  (part  only) 
and  1790.  Various  MS.  transcripts  of  the  whole  book  were  made  in 
the  seventeenth  and  eighteenth  centuries,  apparently  all  1665  or 
later,  and  from  the  Vienna  copy. 

1694.  Wm.  Wotton's  "Reflections  upon  Ancient  and  Modern 
Learning,"  p.  230  quotes  passage  (C.  R.  Murr,  pp.  170,  I.  9  to  I. 
27  inclusive) — given  to  Wotton  by  Dr.  Chas.  Bernard,  who  knew 
only  that  he  had  it  from  a  learned  friend  who  had  himself  copied  it 
from  Servetus.  Wotton's  second  ed.  (cont.  for  first  time  Rich. 
Bentley's  famous  exposure  of  the  "Epistles  of  Phalaris")  has  a 
P.S.  to  the  Preface,  explaining,  p.  XX Vf.,  that  Bernard  received 
the  passage  from  Abr.  Hill,  who  copied  it  from  the  complete  tran- 
script in  the  possession  of  Bishop  John  Moore,  who  has  now  shown 
it  to  W.,  who  prints  further  extracts.  This  transcript  was  made  in 
Cassel  (Mosheim,  p.  344),  was  listed  in  Edw.  Bernard's  Oxford  Cat. 
of  MSS.  in  England  and  Ireland,  1697  (II,  pt.  I,  378,  No.  9848,  mis- 
printed 6848),  and  is  now  in  Cambridge  University  Library  (Cat. 
MSS.  Ill,  320  ;  1858).  I  examined  Hill's  MS.  commonplace  books 
in  the  British  Museum  without  result. 

1 715.  Jas.  Douglas's  BibHogr.  Anat.  Spec,  p.  189,  and  1734, 
p.  104  merely  quotes  Wotton. 

1723.  London  unfinished  reprint  of  the  "  Christianismi  Res- 
titutio" has  Circ.  passage  on  pp.  143-4. 

1728.  (Not  1727)  Allwoerden,  p.  2o6f.,  prints,  from  transcripts, 
longer  passage. 

1763.  De  Bure's  "Bibliographic  Instructive,"  I,  No.  756,  reprints 
Circ.  passage  from  Paris  copy  of  book,  making  it  well  known. 

1 790.  Murr's  reprint,  printed  by  Rau,  Nuremberg,  pp.  1 69f.  on  Circ. 

1892-95.  "Christianismi  Restitutio"  translated  into  German  by 
Spiess  (Wiesbaden,  3  vols.)  the  last  section,  Apol.  to  Melanchthon, 
left  in  Latin.  The  i8g^  id  ed.  of  Vol.  I  is  really  the  same  sheets,  with 
new  title,  but  omits  a  two-page  "Vorwort." 


A  SIMPLE  KEYWORD  SYSTEM  FOR  INDEXING  AND 
CLASSIFYING  CLINICAL  CASE  HISTORIES  AND 
CURRENT  MEDICAL  LITERATURE 

By  William  H.  Mercur,  M.D.,  Pittsburgh,  Pa. 

A  LL  the  ideas  advanced  in  this  article  that  have  any  clinical 
A-^  value  revolve  around  two  central  factors:  First,  the  difFer- 
JL  JLence  existing  between  recollection  and  memory  (see  Diagram 
i);  second,  the  possibility  of  reviving,  clinically,  past  recollections 
as  well  as  past  memories  by  utilizing  a  very  simple  keyword  system 
(see  Diagram  2). 

The  raison  d*etre  for  this  paper  is  the  author's  conviction, 
founded  upon  personal,  as  well  as  practical,  experience,  that  it  is 
f>ossibIe  for  almost  any  busy  practitioner  to  practice  clinical  medi- 
cine much  more  intelligently  and  efficiently,  if  he  will  make  use  of 
the  ideas  here  advanced.  Furthermore,  the  author  believes  that  if 
physicians  who  write  clinical  articles  for  the  medical  profession  will 
utilize,  practically,  the  keyword  idea  and  the  simple  nomenclature 
and  classification  here  advocated,  they  will  succeed  in  convincing 
a  much  larger  circle  of  readers  of  the  truth  of  their  statements  than 
has  hitherto  been  possible. 

We  will  now  discuss  our  first  factor.  Dr.  Charles  W.  Burr,  of 
Philadelphia,  in  an  article  on  "Aphasia,"  which  he  published  in 
The  New  York  Medical  Journal,  May  9,  191 4,  defines  so  beautifully 
and  simply  the  difference  between  recollection  and  memory  that  his 
definitions  are  here  reproduced. 

Recollections.  "The  bringing  into  consciousness  of  things  stored 
in  the  cerebral  cortex.  It  is  a  mental  process,  an  action.  It  should 
never  be  confounded  with  memory." 

Memory.  "Memory  is  a  physical  thing,  and  passive,  and  it  should 
never  be  confounded  with  recollection.  It  is  the  permanent  effect 
of  stimuli  on  brain  and  indeed  on  many  other  cells.  Thought  uses 
memories,  but  memories  are  not  thoughts,  until  recollection  brings 
them  into  consciousness." 

778 


KEYWORD  INDEX  779 

The  great  value  of  our  memory  Is  founded  upon  the  fact  that  our 
intelligence  is  altogether  based  upon  our  faculty  of  memory.  Without 
it,  we  can  keep  no  record  of  experience;  without  experience  to  refer 
to  we  can  form  no  judgments.  Based  upon  the  faculty  of  memory, 
intelligence  is  possible,  and  from  it  all  intelligent  acts  proceed  (Nels 
Quevli).  Hence,  to  be  a  successful  and  intelligent  clinical  practi- 
tioner, one  must  constantly  try  to  learn  from  the  study  of  clinical 
cases,  but  as  it  is  possible  to  recall  at  will  only  a  certain  percentage  of 
our  former  knowledge,  one  should  also  learn  to  appreciate  the  value 
of  being  able  to  file  away  case  records  for  future  reference.  This  ob- 
viates the  necessity  of  learning  the  same  thing  over  and  over  again. 
The  value  of  combining  our  own  personal  experience  with  that  of 
others  as  expressed  in  literature  has  been  beautifully  epitomized 
by  Sir  Wm.  Osler.^  **To  study  the  phenomena  of  disease  without 
books  is  to  sail  an  uncharted  sea,  while  to  study  books  without 
patients  is  not  to  go  to  sea  at  all." 

Our  plan,  in  brief,  offers  to  a  busy  physician  a  simple  method  of 
instantly  reviving  by  means  of  keywords  or  strings  what  his  past 
cases  have  taught  him.  That  is,  he  has  it  in  his  power  to  put  away 
in  the  form  of  a  few  building  stones  for  future  thought  the  more  or 
less  fugitive  memories  of  the  present. 

Although  the  proposed  plan  is  so  simple  in  operation  that  almost 
anyone  can  readily  understand  and  use  it,  a  few  brief  preliminary 
remarks  might  be  of  interest.  In  the  first  place,  it  must  be  evident 
to  every  busy  man  that  he  is  able  to  recall  at  will  only  a  very  small 
proportion  of  what  he  has  really  accomplished  in  the  past,  or  of  those 
things  which  he  daily  sees,  hears,  or  reads.  The  amount  of  informa- 
tion, or  knowledge,  which  any  given  individual  can  recall  at  will 
must,  and  does,  vary  greatly.  For  the  purpose  of  our  present  argu- 
ment, it  can  be  stated  in  a  general  way  that  the  average  man  is  most 
fortunate  if  he  is  able  to  recall  one-tenth  of  his  former  recollections, 
and  that  fully  99  per  cent  of  all  his  memories,  which  he  would  like 
to  recall,  are  not  available  to  him  in  his  daily  work.  Potentially, 
therefore,  as  far  as  our  recollections  are  concerned,  we  are  rarely 
more  than  one-tenth  efficient.  To  most  thinking  people,  the  truth 
of  this  statement  will  be  almost  axiomatic.  Those  who  doubt,  or  who 
desire  further  evidence,  may  be  convinced  if  they  will  give  a  little 

•  "Books  and  Men,"  "i^^quanimitas  and  Other  Addresses,"  1901. 


78o 


KEYWORD  INDEX 


study  to  Diagram  i,  in  which  the  difference  between  recollection  and 
memory  is  graphically  portrayed.  Few  of  us  realize,  unless  we 
have  given  the  matter  some  thought,  how  completely  our  mem- 
ories are  bound  up  and  associated  with  our  thoughts,  and,  fur- 


Mcmoriet  Coadiidaa 

Diagram  i.  Graphic  Representation  of  the  Cycle  of  a  Normal  Thought. 

thermore,  we  do  not  realize  that  a  thought  on  any  subject,  which 
usually  flashes  into  our  minds  and  out  again  with  such  marvelous 
rapidity,  instead  of  being  an  undivided  unit,  can,  from  a  mechanical 
standpoint,  easily  be  divided  into  three  distinct  parts.  All  our  sensory 
impressions,  from  which  our  thoughts  are  derived,  can  reach  our 
brains  in  only  one  of  two  ways — first,  by  means  of  our  five  senses, 
singly  or  combined,  and  second,  from  memories  of  past  sensations. 

Diagnosis  Treatment 

1.  Symptoms    Road 

2.  Etiological    Road 

3.  Anatomical  or  Sys- 
Diagnosis-  tems  Road 

4.  Pathological  or  Lab- 
oratory Road 

5.  Differential  Diagno- 
sis Road 

Diagram  2.  Graphic  Representation  Keyword  System. 

Diagram  2  represents  the  course  of  a  normal  complete  thought 
as  consisting  of  three  parts:  First,  a  stream  flowing  into  a  lake; 
second,  the  lake  into  which  it  flows,  and  third,  another  stream  as  an 
outlet  of  this  lake. 


-Treatment. 


KEYWORD  INDEX  781 

The  stream  flowing  into  the  lake  represents  the  sensory  birth 
of  a  thought;  the  lake  its  cortical,  or  gray  matter  hfe;  and  the  stream 
which  emerges  from  this  lake  represents  what  occurs  to  a  thought 
after  being  acted  upon  by  the  gray  matter  of  the  individual,  and  is 
referred  to  in  our  diagram  as  a  motor  discharge.  That  is,  we  must 
first  arrive  at  a  conclusion  before  we  can  translate  it  into  some  form 
of  action.  Hence,  not  only  must  all  of  our  thoughts  have  a  sensory 
birth,  but  nature,  in  order  to  conserve  our  energies,  is  also  kind 
enough  to  index  our  thoughts,  more  or  less  mechanically,  when  they 
reach  our  brain;  i.e.,  similar  sights,  sounds,  tastes,  etc.,  index  or 
associate  themselves  with  other  previous  and  similar  sensations. 

The  progress  of  a  thought  through  this  simple  diagram  can  be 
simply  illustrated,  if  one  will  imagine  that  he  has  just  experienced 
the  birth  of  a  thought  that  he  has  never  had  before.  Naturally  this 
thought  does  not  associate  itself  with  any  previous  thought,  so  it 
would  have  to  take  a  place  by  itself  as  thought  one,  illustrated  in 
diagram  as  hne  No.  i.  Later,  as  so  frequently  occurs,  a  similar 
thought  will  be  born,  and  now  thought  two  associates  itself  with 
thought  one.  To  make  our  illustration  a  little  more  clear,  imagine 
the  birth  of  three  more  similar  thoughts,  or  a  total  of  five,  which  all 
line  up  together  in  our  cortex.  Now,  without  really  wishing  to  think, 
one  is  practically  forced  to  do  so,  in  order  to  explain  what  this  suc- 
cession of  events  really  means.  An  individual  now  takes  a  certain 
portion  of  his  daily  time,  which  can  never  exceed  twenty-four  hours, 
and  associates  it  with  a  certain  amount  of  his  gray  matter,  and  sooner 
or  later  reaches  a  conclusion  indicated  by  a  line  in  our  diagram. 
The  reason  for  arriving  at  a  conclusion  is  that  we  may  be  able  to 
translate  our  thought  into  some  form  of  action.  Our  final  conclusion 
is  then  discharged  through  the  outlet  of  our  lake.  Thus  the  normal 
cycle  of  a  thought  is  completed. 

To  illustrate  further — one  hears,  suddenly,  a  dangerous  sound; 
it  at  once  associates  itself  with  former  dangerous  sounds  and  one 
jumps.  Sensory  birth,  cortical  Hfe,  and  motor  discharge  follow  each 
other  in  logical  but  rapid  succession.  Our  diagram  will  further 
enable  the  reader  to  understand  that,  as  it  is  quite  evident  that  no 
one  can  either  eat  or  sleep  for  another,  so  also  no  one  else  can  either 
think  through,  or  have  a  motor  discharge  for,  another.  The  chief 
difi"erence  between  our  memories  and  our  recollections  (Diagram  i) 


782  KEYWORD  INDEX 

is  that  our  memories  remain  indexed  in  our  cortical  life,  but  our 
recollections,  which  indicate  something  we  have  thought  through 
and  translated  into  action,  are  represented  by  the  dry  bed  of  the 
stream  of  the  motor  discharge.  Furthermore,  if  one  considers  the 
enormous  number  of  sensory  impressions  which  not  only  flow  daily 
into  our  cortex,  but  have  been  doing  so  daily  since  our  birth,  it  is 
self-evident  that  no  one  could  possibly  hope  to  arrive  at  any  definite 
conclusion  or  have  a  motor  discharge  except  for  a  small  proportion 
of  such  impressions. 

Although,  usually,  it  is  a  comparatively  easy  matter  for  one  to 
recall  certain  circumstances,  it  is  always  a  most  difficult  matter  to 
reassemble  our  past  memories,  when  one  has  the  time  and  the  clin- 
ical case  with  which  to  utilize  them. 

The  keyword  system,  here  advocated,  was  devised,  or  rather 
grew  out  of,  the  necessity  of  the  author's  having  to  index  and  file 
away  in  a  simple  manner,  not  only  his  own  case  histories,  but  also 
to  index  a  very  large  transportable  reprint  library,  which  he 
utilizes  in  his  consultation  practice.  It  was  founded  and  evolved 
upon  ideas  which  he  got  principally  from  three  sources.  The  author 
wishes  first  of  all  to  express  his  deep  gratitude  to,  and  his  great 
admiration  for.  Dr.  J.  L.  Whitney,  of  San  Francisco,  for  the  aid 
which  he  has  given  him  in  his  little  book,  "List  and  Classifications 
of  Diagnosis,"  which  was  prepared  for  the  use  of  the  University  of 
California  Hospital.  Without  the  aid  of  Dr.  Whitney's  book  this 
paper  could  not  have  been  written.  Dr.  Whitney  suggests  a  very 
simple  plan  for  filing  away  all  case  histories  with  either  an  etiological 
or  an  anatomical  diagnosis.  Nothing  that  the  author  has  ever  seen 
could  be  better  adapted  for  this  purpose.  As  it  was  devised,  primarily, 
for  diagnosis  only,  it  did  not  lend  itself,  except  partially,  to  the 
filing  away  of  recent  medical  literature.  To  overcome  this  difficulty, 
the  author  obtained  the  classification  used  in  the  Index  Medicus 
from  the  editor  of  that  periodical.  In  order  to  simplify  matters,  and 
not  to  have  any  overlapping  of  the  keywords  used  in  the  Whitney 
classification,  the  author  crossed  out  of  the  Index  Medicus  key- 
word system  everything  which  Dr.  Whitney's  book  covered,  both 
etiologicallyand  anatomically.  No  better  illustration  of  the  wonderful 
simplicity  and  value  of  Dr.  Whitney's  classification  could  be  given 
than  the  fact  that  when  this  work  was  completed  there  was  barely 


KEYWORD  INDEX  783 

I  per  cent  left  of  the  Index  Medicus  classification.  This  now  gave 
the  author  a  foundation  to  build  on  in  simplifying  his  methods  of 
filing  away  case  records  and  current  medical  literature,  but  it  by 
no  means  solved  the  practical  aspects  of  his  problem,  as  the  resulting 
keywords,  although  scientifically  correct,  were  still  far  too  numer- 
ous to  be  handled  in  a  simple  manner.  At  this  time  the  author 
heard  of  a  new  scientific  classification  which  had  been  recently 
installed  in  the  Allegheny  County  Law  Library,  by  their  clever 
librarian,  Mr.  J.  Oscar  Emrick.  His  predecessor,  who  did  not  con- 
sider a  catalogue  necessary,  and  who  was  known  far  and  near  as  the 
"Human  Catalogue,"  died,  leaving  to  Mr.  Emrick  a  unique  oppor- 
tunity of  devising  a  scientific  modern  catalogue  for  an  enormous 
law  library  without  being  hampered  by  any  traditions.  As  a  basis  for 
his  work  of  scientific  classification,  he  finally  adopted  the  American 
Digest  System.  This  starts  out  with  the  question.  What  does  law 
do  clinically  for  the  public?  The  simple  conclusion  reached  is:  All 
that  law  can  or  does  do  for  the  public  can  be  classified  or  grouped 
under  seven  basal  headings.  By  subdividing,  scientifically,  these  seven 
headings,  412  keywords  work  out;  and  under  these  412  keywords 
anything  that  an  attorney  might  want  in  the  way  of  text  books, 
references,  legal  decisions,  or  miscellaneous  information  may  be 
readily  found.  It  is  a  wonderful  experience  to  consult  this  library 
and  to  find  that  in  barely  fifteen  minutes  a  vast  amount  of  infor- 
mation is  available  to  the  reader.  The  author  then  tried  to  apply 
the  same  scientific  principle  to  clinical  medicine,  with  the  following 
results.  He  asked  himself.  What  does  clinical  medicine  do  for  the 
public?  The  answer  is:  A  physician  first  clinically  diagnoses,  then 
treats,  the  public. 

Clinical  medicine,  therefore,  begins  with  diagnosis  and  ends,  or 
should  end,  with  treatment.  Clinically  speaking,  and  the  suggested 
classification  is  off"ered  purely  as  a  clinical  one,  there  are  only  five 
possible  logical  and  scientific  roads  which  a  man  can  travel  if  he 
wishes  to  make  a  diagnosis.  (Diagram  2.)  The  first  is  the  Road  of 
Symptoms.  Clinical  experience  has  demonstrated  that  patients 
rarely  come  to  a  physician  for  diagnosis  or  treatment  unless  they 
have  symptoms,  and  if  these  are  carefully  collected  and  analyzed,  a 
primary  diagnosis  can  usually  be  made  in  about  60  per  cent  of  cases. 
Frequently,  however,  the  symptoms  are  too  few  in  number,  or  they 
are  too  vague  in  character,  to  make  a  diagnosis,  and  the  observer 


784  KEYWORD  INDEX 

now  finds  this  road  blocked.  The  second  logical  road  presents  itself 
as  the  etiological  road,  a  road  which  permits  of  very  few,  but 
definite,  subdivisions,  such  as  Infectious  Diseases,  Diseases  Due  to 
Poisons,  Animal  Parasites,  etc.  If  this  second  road  is  blocked,  the 
third  logical  road  is  the  Regional,  or  the  Anatomical  road,  which 
has  been  most  beautifully  outlined  and  classified  by  Dr.  Whitney. 
If,  again,  we  find  this  road  blocked,  we  can  logically  travel  the  fourth 
road:  the  Pathological,  or  Laboratory  Road;  and  if  by  this  time  the 
above  four  roads  do  not  lead  us  to  a  diagnosis,  we  find  but  one  road 
left  to  use:  the  fifth,  or  Diff'erential  Diagnosis  Road.  By  traveling 
any  one  or  all  of  these  five  roads,  and  the  author  knows  no  others, 
we  must  logically  arrive  at  our  disease,  or  at  No  Disease,  or  at  No 
Diagnosis.  In  any  event,  we  must  now  treat  the  case.  If  a  disease, 
we  should  treat  it,  if  at  all  possible,  etiologically;  if  this  is  not  pos- 
sible, it  must  be  treated  anatomically  or  symptomatically.  If  No 
Disease,  it  must  be  treated  psychically,  and  if  No  Diagnosis,  it  must 
be  treated  symptomatically  until  a  diagnosis  can  be  made  or  the 
patient  leaves  us  for  someone  who  can  make  a  diagnosis. 

Now  for  the  most  practical  part  of  this  paper.  After  a  physician 
has  made  a  diagnosis  of  any  given  case,  all  he  has  to  do  is  to  index 
it,  together  with  the  complications  associated  with  it,  either  etio- 
logically or  anatomically,  following  the  Whitney  classification.  If, 
later,  when  one  wishes  to  utilize  it,  it  is  not  found  alphabetically 
under  one  heading,  it  must  be  under  the  other.  One  cannot  go  wrong. 
The  above  covers  the  simple  indexing  of  the  first  valuable  source  of 
our  cHnical  knowledge — our  case  histories.  To  index,  now,  the  memo- 
ries of  our  second  valuable  source  of  current  knowledge;  first  index 
and  file  them  away  under  the  name  of  the  disease,  as  you  will  after- 
wards want  to  use  them.  As  an  illustration,  assume  that  you  had  just 
read  something  new  about  Influenza.  Under  the  heading  Influenza, 
Diagnosis  of,  you  file  away  for  future  use,  under  our  five  keywords, 
anything  you  have  read,  and  wish  later  to  recall,  that  is  applicable 
to  the  Symptoms,  Etiology,  Anatomy,  Pathology  or  New  Laboratory 
Tests,  or  points  in  Diff'erential  Diagnosis,  concerning  Influenza. 
No  difficulty  will  be  found  in  filing  away  all  your  information  under 
these  five  simple  keywords  or  their  logical  subdivisions.  When,  later, 
you  want  to  use  this  information,  you  simply  pull  one  of  these  five 
strings.  The  practical  clinical  advantage  of  this  plan  is  that  it  brings 
together,  at  the  same  place  and  time,  all  one  wishes  to  recall  about 


KEYWORD  INDEX  785 

past  similar  cases,  and  assembles  for  you  when  you  wish  to  use  it, 
in  the  form  of  building  stones  of  thought,  all  the  new  ideas  which 
might  help  you.  When  one  considers  the  rapidity  with  which  new 
ideas  are  constantly  accumulating,  it  is  a  great  advantage  not  to 
assemble  these  in  advance  of  the  actual  case,  as  the  newer  data 
may,  and  often  do,  change  all  of  our  former  conclusions.  This  is 
one  of  the  especial  time-saving  factors  of  the  proposed  plan.  Why 
build  a  house  in  advance  of  the  time  you  are  going  to  occupy  it? 
Save  your  gray  matter  and  economize  your  time. 

The  author  feels  that  the  reason  why  this  simple  keyword  system 
has  not  been  more  extensively  adopted  is  that  no  one  thought  that 
such  a  complicated  and  involved  problem  as  the  one  we  are  dealing 
with  could  be  solved  in  such  a  simple  manner.  Most  of  our  problems 
are  really  very  simple  in  their  essence  when  we  really  understand 
them,  but  are  most  puzzling  and  complicated  when  we  do  not.  It 
is  not  at  all  surprising  that  if  a  man  thought  that,  in  order  to  recall 
or  remember  certain  things,  he  would  have  to  classify  and  put  them 
away  in  about  a  thousand  different  places,  he  should  at  once  be- 
come discouraged  and  give  up  the  problem  as  insoluble.  But  if  he 
could  be  shown  a  simple  way  of  putting  all  these  thousand  things 
away  under  only  five  simple  headings,  he  would  not  likely  regard 
his  problem  as  being  quite  so  hopeless. 

The  average  man  should  not  be  too  busy,  if  he  is  at  all  inclined 
to  be  systematic,  to  do  all  the  necessary  work  involved  in  carrying 
the  proposed  plan  for  himself;  but  if  he  is  too  busy,  or  too  unsyste- 
matic to  do  so,  he  can  easily  employ  someone  to  do  it  for  him,  as 
the  principles  involved  are  so  simple  that  they  can  easily  be  taught 
to  almost  any  intelligent  person. 

The  success  of  any  scientific  keyword  system  is  founded,  largely, 
upon  the  well-known  psychological  fact  that  when  once  our  per- 
ceptions and  ideas  are  welded  together  in  our  consciousness,  they 
tend  to  persist  and  are  easily  recalled.  The  author,  in  order  to  make 
this  simple  plan  practical,  has  combined  the  keywords  of  the  Whit- 
ney Classification  with  those  of  the  Index  Medicus,  and  has  had  all 
these  keywords  mounted  and  arranged  alphabetically  on  cards. 
All  minor  subdivisions  which  these  few  keywords  do  not  provide 
may  easily  be  added,  when  necessary,  as  the  index  and  material 
grow,  by  merely  following  the  etiological  and  anatomical  subdi- 
visions of  Dr.  Whitney. 


PROTHYMIA:    NOTE   ON   THE    MORALE-CONCEPT 
IN  XENOPHON'S  "CYROPEDIA"* 

By  E.  E.  Southard,  M.D.,  ScD., 

BuIIard  Professor  of  Neuropathology,  Harvard  Medical  School;  Late  Major,  Chemical 
Warfare  Service,  U.  S.  Army 

Cyrus.  To  put  enthusiasm  (ri  irpoBvixtav  kn^oKtiv)  into  troops,  nothing  seems 
to  work  better  than  inspiring  them  with  hopes. 

Camhyses.  Son,  that  would  be  like  a  hunter's  calling  his  dogs  all  the  time  with 
game  calls.  At  first  they  obey  eagerly  {irpoBiixijn).  But,  if  he  fools  them  too  often,  they 
won't  answer  even  if  the  game  is  there. 

THIS  passage  is  part  of  a  long  and  well-balanced  discussion 
on  the  art  of  war,  a  talk  between  Cyrus  and  his  father, 
Cambyses,  before  Cyrus  goes  to  war,  in  the  "Cyropedia" 
(I,  VI,  19).  Protbymia  {ii  TzpoBv^la)  is  a  leading  term  in  Xenophon 
for  some  aspects  of  what  we  have  come  to  call  morale.  Several 
morale-making  procedures  of  the  constructive  (or  protbymic)  group 
are  acutely  discussed  in  the  "Cyropedia,"  often  occurring  in 
Socratic  talks  between  the  Persian  paragon,  Cyrus,  and  his  gen- 
erals. It  cannot  be  denied  that  Xenophon  himself,  as  the  great 
specialist  in  retreat,  was  a  master  of  morale.  Into  his  Admirable 
Crichton,  Cyrus,  it  is  supposed  that  the  great  military  philosopher 
contrived  to  insert  virtually  all  the  great  qualities  of  generalship 
of  Xenophon's  own  associates,  the  real  younger  Cyrus  and  the 
Spartan  kings,  Agesilaus  and  Clearchus,  as  well  as  of  his  teacher, 
Socrates,  and  of  Xenophon  himself.  It  is  said  that  the  Romans, 
such  as  Cato,  Cicero,  and  the  younger  Scipio,  highly  valued  the 
"Cyropedia"  as  a  sort  of  military  vade  mecum.  The  Athenians 
did  not  like  it  too  well,  because  in  the  Persian  picture  they  saw 
all  too  clearly  the  Spartan  outlines.  If  a  history  of  the  morale- 
concept  were  to  be  written  (and  this  would  be  a  rewarding  task  as 
compared  with  much  that  goes  as  ethical  discussion  nowadays), 

*The  Committee  on  Contributions  to  the  Osier  Anniversary  Volume  requests 
additions  to  knowledge  based  on  research  in  some  branch  of  medical  or  biological 
science.  The  writer  hopes  that  his  excursion  into  antiquity  may  be  so  regarded.  The 
work  was  a  by-product  of  study  in  connection  with  the  Chemical  Warfare  Service, 
the  service  which,  of  all  military  branches,  had  primarily  to  deal  with  morale. 

786 


MORALE-CONCEPT  IN  "CYROPEDIA"  787 

the  "Cyropedfa**  would  take  no  small  part  in  the  history  of  morale 
in  antiquity. 

Below  I  shall  itemize  the  morale  measures  or  protbymic  proce- 
dures proposed  by  Xenophon  in  the  "Cyropedia."  But  I  wish  to 
dwell  a  moment  on  the  significance  that  underlies  the  terms 
protbymia  and  protbymic  as  used  of  constructive  morale.  Terms 
ending  in  -tbymia  have  become  rife  in  the  literature  of  some  of  the 
mental  sciences,  especially  in  that  of  mental  diseases,  and,  I  believe, 
should  come  into  more  general  use  in  the  broader  range  of  the 
literature  of  the  moral  and  even  the  political  sciences.  Morale  takes 
a  prominent  place  in  what  might  be  called  military  ethics,  to  say 
nothing  of  the  science  or  art  of  strategy.  But  we  all  now  have 
ringing  in  the  backs  of  our  heads  the  James  phrase,  "moral  equivalent 
of  war" — we  are  all  quite  sure  that  in  the  coming  struggle  between 
nationalism  and  groupism  the  most  gigantic  hinges  of  fate  are 
going  to  turn  on  morale.  But  what  is  morale?  A  nomenclature  and 
algebra  of  discussion  is  lacking.  Hence  I  suggest  this  ancient  term 
protbymia,  for  some  aspects  of  morale,  heedless  of  whether  more 
questions  are  raised  than  settled  thereby. 

As  we  examine  below  the  morale  suggestions  of  Xenophon, 
let  us  bear  in  mind  the  trend  of  a  leading  term  like  protbymia. 
Such  current  terms  (e.g.,  in  psychiatric  literature)  as  bypertbymia, 
bypotbymia,  cyclotbymia,  paratbymia,  all  refer  to  some  quantitative 
or  qualitative  aspect  of  the  emotional  life.  Any  term  ending  in 
'tbymia  turns  toward  the  emotional  or  affective  side  of  the  mental 
life,  as  the  analogous  terms  ending  in  -pbrenia  (e.g.,  scbizopbrenia, 
parapbrenia)  turn  toward  the  intellect;  terms  ending  in  -boulia 
toward  the  will;  and  the  long  familiar  terms  ending  in  -estbesia 
toward  the  senses.  Protbymia,  then,  for  ourselves  as  well  as  for  the 
Greeks,  is  a  term  which  commits  the  users  to  a  more  or  less  definitely 
emotional  theory  of  morale.  The  ending  -tbymia  refers  to  dv/ids, 
originally  the  heart,  but  by  transference  used  (as  we  ourselves 
still  use  the  term  "heart")  for  the  emotions  of  a  man. 

The  term  protbymia,  then,  draws  us  definitely  away  from  the 
intellect  and  the  senses  that  supply  the  intellect,  and  draws  us 
definitely  toward  the  emotions  and  the  will,  which  we  commonly 
account  to  be  controlled  by  the  emotions.  Although  we  admit  that 
morale  might  sharpen  the  senses  (byperestbesia),  and  increase  the 


788  MORALE-CONCEPT  IN  "CYROPEDIA" 

rate,  range,  and  accuracy  of  the  intellect  (a  process,  as  one  might 
say,  of  byperpbrenia),  and  still  more  readily  increase  the  force 
and  celerity  of  the  will  (a  sort  of  byperboulia),  yet  the  use  of  the 
term  protbymia  would  tend  to  commit  us  to  a  certain  primacy  of 
the  emotions  (some  sort  of  bypertbymia)  in  all  this.  Do  we  mean 
that  the  process  of  morale-making  is  predominantly  through  the 
emotions,  with  the  resultant  morale  something  possibly  in  itself 
not  emotional  at  all?  Or  do  we  mean  that  morale  is  a  state  of  the 
soul  in  which  emotion  is  the  great  ingredient?  Does  the  emotion 
bound  up  in  morale  come  by  way  of  cause  or  in  the  shape  of  effect? 
Shall  we  use  emotion  to  explain  the  origin  of  morale  or  to  describe 
its  character  once  established? 

Re  Xenophon's  above  passage  on  morale  or,  as  you  might  say, 
on  protbymics,  Cambyses  was  talking  with  his  son,  Cyrus.  They 
agreed  that  generalship  was  not  all  tactics — that  supplies  and 
health  and  physical  training  were  indispensable  too.  Then  the 
youthful  Cyrus  advanced  that  too  naive  theory  of  morale  which 
was  bowled  over  by  Cambyses,  who  continued: 

So  with  soldiers'  hopes.  If  you  raise  false  expectations  too  often, 
you  will  not  be  believed  even  when  the  hopes  are  well  grounded.  Son, 
you  should  refrain  from  saying  what  you  are  not  perfectly  sure  of.  You 
may  effect  your  purpose  by  making  others  your  mouthpiece.  Faith  in  your 
own  personal  words  of  encouragement  (irapaxiXevsLs),  you  must  keep 
absolutely  sacred  to  serve  you  in  the  greatest  crises. 

Thus  early  was  raised,  as  I  indicate  by  italicizing  a  sentence 
above,  the  question  whether  in  the  protbymic  (morale-engendering) 
process  one  ought  not  to  connive  at  the  inspiration  oi  false  hopes 
through  allowing  subordinates  to  tell  untruths.  Cambyses  and  Cyrus 
had  apparently  no  doubt  of  this. 

Having  considered  tactics,  supplies,  hygiene,  physical  training, 
and  morale,  father  and  son  speed  on  to  questions  of  discipline  and 
of  the  manifold  process  of  out-tricking  the  enemy,  not  forgetting 
in  the  end  the  profit  that  attends  obeying  the  gods.  As  for  what  I 
have  called  out-tricking  the  enemy,  there  is  some  material  for 
morale  discussion  there  also.  Xenophon  calls  out-tricking  the  enemy 
pleonexia  {TrXeovi^la,  form,  rd  ir\kov  excoVy  having  more,  i.e., 
getting  advantage),  and  Xenophon  makes  Cyrus  and  Cambyses 


MORALE-CONCEPT  IN  "CYROPEDIA"  789 

have  a  little  tilt  on  whether,  in  order  to  learn  to  out-trick  the 
enemy,  one  should  not  have  practice  in  out-tricking  one's  friends. 
The  decision  is  against  the  use  oipleonexic  practice  on  one's  friends, 
though  at  the  age  of  twenty-six  or  twenty-seven  (which  age  Cyrus 
had  now  reached)  it  seemed  safe  (to  Cambyses)  to  teach  men  how 
tricks  like  those  used  in  hunting  and  trapping  animals  might  be 
used  towards  men,  one's  enemies. 

As  for  the  more  strictly  protbymic  methods  of  Cyrus  (i.e.,  of 
Xenophon,  perhaps),  let  us  proceed  to  our  analysis.  There  is  an  in- 
teresting passage  in  which  mere  exhortation  is  discounted,  the 
value  of  previous  training  extolled,  and  the  results  of  war  cries 
and  cheering  told.  So  was  the  army  of  Cyrus  filled  with  enthusi- 
asm (TTpo^u/xta),  emulation  (^tXortAita),  strength  (pco/xr;),  courage 
(ddppos),  good  cheer  {irapaKtXevcryLbs),  self-control  {ao)(j>po<TVvr)), 
obedience  (Tret^w).  Courage  in  the  form  of  fihos  and  eagerness 
to  close  with  the  enemy  (r6  aTevdeLv  (Tvufil^ai)  appeared  later  in 
the  contest  with  the  Assyrians.  More  war-cries  from  Cyrus,  and 
the  Assyrians  fled  (III,  iii,  49-58). 

Another  practical  protbymic  procedure  is  hinted  at  in  the  sug- 
gestion (VI,  ii,  33)  that  we  wbet  our  minds  wben  we  wbet  our  spears. 

The  most  practical,  or  at  all  events  the  most  beautiful,  procedure 
is  naturally  that  of  the  Queen  Panthea — witness  that  most  pro- 
tbymic speech  of  VI,  iv,  5-7,  and  the  kiss  of  her  lips  on  the  chariot- 
box  of  King  Abradatas,  going  to  his  death. 

Before  undertaking  an  analysis  of  these  various  protbymic  pro- 
cedures of  Xenophon,  let  us  consider  some  modern  conceptions  of 
morale,  or  at  least  such  deposit  of  wisdom  as  can  readily  be  scraped 
from  the  maxim  collections.  Napoleon  advised  maneuvering  about  a 
fixed  point  only:  we  have  chosen  the  ancient  contribution  of  Xeno- 
phon as  such  a  possible  fixed  point.  How  would  the  moderns  agree 
with  Xenophon? 

Morale,  according  to  Murray,  is  a  moral  condition,  or  conduct, 
or  behavior,  especially  with  regard  to  confidence,  hope,  zeal,  sub- 
mission to  discipline.  The  relations  of  morale  to  ethics  and  psy- 
chology are  plain,  and  the  reference  to  the  science  of  war  is  hardly 
less  constant  in  our  usage — a  usage  in  English  less  than  a  century 
old  and  a  frequent  usage  perhaps  less  than  half  a  century  old.  Yet 
on  virtually  every  page  of  a  book  like  Marshal  Foch's  "Principles 


7^  MORALE-CONCEPT  IN  "CYROPEDIA" 

of  War"  is  some  consideration  or  other  bearing  directly  on  morale. 
Hardly  a  commander  but  would  now  acknowledge  the  supremacy 
of  morale  in  warfare,  and  the  more  so  in  the  modern  nationalistic 
warfare  that  followed  Carnot  and  Napoleon.  But  is  there  a  science 
of  morale?  Or,  if  there  is  not  now  a  morale-science  in  esse,  is  there 
not  one  in  posse,  when  the  history  of  the  Great  War  comes  to  be 
written  and  all  the  motives  show  forth  in  relief?  Let  us  bear  in  mind 
a  useful  point  of  Marshal  Foch  himself:  That  there  is  no  science  oj 
waff  but  only  an  art!  Probably  the  same  may  prove  true  of  the  es- 
sence of  .war,  the  behavior  called  morale.  Even  if  we  should  obtain 
a  fixed  point  of  discussion  by  a  survey  of  ethics,  psychology,  and 
polemics,  we  should  still  have  to  stick  to  an  old  saying  of  Lepelletier 
de  la  Sarthe,  Dans  la  culture  du  moral,  jaites  toujours  marcher 
Viducation  du  caeur  avant  celle  de  V esprit.  Morale  then  belongs  more 
to  the  heart  than  the  head,  and  the  task  of  a  rational  or  scientific 
or  methodical  morale  must  seem  as  ridiculous  to  the  soldier  as  a 
plan  to  use  the  stethoscope  in  a  case  of  Sursum  Corda. 

The  fixed  point  of  maneuver  in  morale,  let  us  say,  then,  is  the 
heart  and  not  the  head.  And  by  heart  we  shall  freely  mean  a  good 
deal  more  that  lies  in  the  thorax,  and  perhaps  also  the  blood  and 
brawn  and  much  that  passes  under  the  name  of  physique.  Perhaps 
we  should  not  go  so  far  as  did  Cabanis  and  say  that  morale  is  nothing 
but  physique  from  a  special  point  of  view.  Nor  should  we  take  too 
literally  the  grinning  Voltaire  with  his  "/e  physique  gouverne  toujours 
le  moral/'  much  as  we  should  like  to  condemn  this  friend  of  Frederick 
the  Great  for  his  own  morale,  doubtless  based  on  his  own  scanty 
physique.  Morale  will  be  a  matter  of  the  heart  more  than  of  the 
head,  more  even  of  the  belly  and  the  members  than  of  the  head. 
Morale  will  stand  less  opposed  to  physique  than  to  the  psychic  part  of 
the  man.  These  are  some  of  the  points  that  crowd  into  our  minds 
when  someone  proposes  a  morale-science,  a  rationalization  and 
formulation  of  the  morale-problem,  to  the  possible  end  of  propa- 
ganda. One  stands  in  awe  of  dished-up  formulae,  of  pumped-up 
morale,  like  the  poor  appealing  patient  with  her  plaint  to  the  doctor, 
"Please  don't  try  any  of  your  psychotherapy  on  me  I"  And  just  as 
the  morale-pumpers  can  be  too  cerebral,  so  can  they  rely  too  much 
on  physique:  it  was  an  acute  remark  with  some  measure  of  truth 
that  Rousseau  made,  "5t  le  physique  va  trop  bien,  le  moral  se  cor- 


MORALE-CONCEPT  IN  "CYROPEDIA"  791 

rompt.**  The  cultivation  of  morale  by  any  extrinsic  means  strikes 
us  as  nigh  to  a  species  of  corruption,  and  propaganda  seems  closely 
allied  to  fake. 

Our  difficulties  with  morale  then  are  (a)  of  definition,  partly 
intrinsic,  partly  (b)  due  to  the  recent  introduction  of  the  term  into 
English,  a  term  (c)  which  in  French  antedates  nationalistic  warfare 
in  the  Napoleonic  sense,  and  which  (d)  has  no  corresp>onding  Latin 
or  Greek  term  by  which  the  mutable  modern  usages  could  be 
controlled  and  at  last  fixed.  It  is  unlikely  that  the  intrinsic  difficulties 
of  the  morale-concept  will  be  resolved  until  we  can  arrive  at  better 
definitions  of  the  concept  itself.  It  was  in  a  search  for  such  definitions 
that  I  came  upon  the  "Cyropedia." 

Now,  the  "Cyropedia"  manifestly  contains  much  that  bears 
on  the  modern  morale-concept.  Manifestly,  also,  however,  the 
"Cyropedia"  could  not  foresee  the  French  Revolution  and  the 
developments  of  nationalistic  warfare  that  followed.  Accordingly, 
the  list  of  morale  measures  to  be  found  in  a  work  of  Xenophon  can- 
not be  exhaustive.  I  have  preferred,  therefore,  to  use  Xenophon*s 
leading  term  protbymia  as  a  general  caption  for  a  certain  group  of 
constructive  morale  measures. 

Following  is  a  list  of  morale  or  protbymic  factors  occurring 
more  or  less  prominently  in  Xenophon's  "Cyropedia."  I  present  a 
rough  subdivision  of  these  according  to  the  predominance  of 
emotional  or  of  volitional  ingredients: 

PROTHYMIC  FACTORS 

Emotional  Volitional 

Hope  Emulation  i<j>i\oTiiila) 

Enthusiasm  (xpodvula)  Strength  (viifxr)) 

Good  cheer  (rapaxtXtvtitit)  Self-control  {aru}<f>pooini) 

Courage  {Oippot,  ftivot)  Obedience  (xtiBd) 

Woman-in-mind  (episode  of  War-cries  and  singing 

Panthea  and  Abradatas)  Desire  to  grapple  {r'o  ffxtiSttp  vvnnl^ai) 

Spear-whetting 

It  may  be  asked  whether  the  intellectual  side  of  morale  is  not 
unduly  neglected  by  Xenophon — a  large  question.  More  narrowly 
speaking,  is  there  a  degree  of  intellectuality  in  some  of  the  morale- 
factors  which  Xenophon  does  enumerate — a  side  deliberately  ig- 
nored in  such  a  forced  classification  as  that  here  made?  Does  not 
emulation  imply  some  more  or  less  rational  object  of  rivalry?  Do 
not  self-control  and  obedience  necessarily  refer  to  the  reason?  If 


792  MORALE-CONCEPT  IN  "CYROPEDIA" 

one  is  a  state  of  hope,  or  if,  like  King  Abradatas,  one  goes  to  battle 
with  the  Queen  Panthea's  kiss  on  (a)  lips,  (6)  armor,  and  (c)  chariot- 
box,  is  not  one  by  just  so  much  a  rationalist  and  above  the  brutes? 
Perhaps;  but  the  point  of  the  analysis  here  is  not  to  trace  the  genesis 
of  sundry  mental  states  so  much  as  to  find  those  mental  states 
whose  induction  makes  for  morale.  To  that  end,  few  will  doubt  the 
value  of  suppressing  intellect  and  stressing  emotional  and  volitional 
states  of  morale,  regardless  of  the  technique  of  their  bringing-about. 
The  point  comes  out  most  plainly  in  an  analysis  of  war-cries,  which 
surely  work  more  or  less  regardless  of  the  degree  of  intelHgence  used 
in  their  construction. 

But  there  is  still  greater  and  perhaps  more  important  doubt 
whether  some  of  these  protbymic  factors  are  not  wrongly  placed  in 
the  emotional  or  volitional  columns.  Of  course  behaviorists  might 
regard  the  distinction  between  emotions  and  will  itself  as  forced 
and  unnecessary:  that  question  can  evidently  not  be  answered  with 
such  limited  material  as  we  now  possess.  On  the  other  hand,  some 
beheve  that  every  act  is  so  dependent  on  emotion  that  (for  quite 
an  opposite  reason)  the  distinction  between  emotions  and  will  has 
always  been  too  sharply  drawn.  Without  taking  issue  with  either 
the  behaviorists,  or  the  emotional  monists,  we  may  still  profitably 
preserve,  on  this  practical  level,  a  rough  distinction  between  emo- 
tions and  will. 

In  fine,  the  "Cyropedia"  of  Xenophon  has  at  the  least  a  large 
historical  interest  re  morale,  because  Xenophon  not  only  was  a  great 
general  and  specialist  in  the  morale  of  retreat,  but  also  could  express 
in  the  historical  novel  and  tract  called  "Cyropedia"  a  number  of 
conceptions  freed  from  the  prejudice  of  politics.  The  picture  was,  to 
be  sure,  more  Spartan  than  Athenian,  and  not  especially  Persian; 
nevertheless  the  Romans  found  the  ideas  of  the  "Cyropedia"  per- 
manently inspiring.  Anything  written  before  the  French  Revolu- 
tion must  either  be  very  final  or  not  at  all  final.  The  "Cyropedia" 
shows  a  little  of  both  qualities.  * 

Many  of  the  morale  measures  of  the  "Cyropedia"  fall  under  the 
general  head  of  protbymia,  a  term  derived  from  dvjx6s,  the  Greek 
word  for  strong  feehng  and  passion,  corresponding  with  the  Latin, 
animus.  Homer  placed  the  origin  of  dvfids  in  the  chest  or  sometimes 
in  the  midrifi"  (of  course,  dvfids,  animus^  is  sharply  distinguished 


MORALE-CONCEPT  IN  "CYROPEDIA"  793 

from  dvfjLos,  tbymus,  or  sweetbread).  As  was  above  stated,  the  ending, 
-tbymia,  is  coming  rapidly  into  psychiatric  usage  for  qualities  or 
degrees  of  emotional  disorder.  Plato  even  began  the  habit  of  -tbymia 
compounds,  when  he  distinguished  cTrt^u/zto;,  appetite,  from 
dviJ.6s,  spirit  or  passion.  The  irpo-  of  TrpoOvfiia  probably  signifies 
readiness  or  wilhngness,  and  suggests  pushing  forward  in  space. 
But  Ovfids  is  also  a  term  implying  much  activity  {dvcc — rushing, 
excitement,  or  burning).  If,  then,  dviJ,6s  and  its  derivatives  are  to 
relate  to  emotions,  it  must  be  conceded  that  the  behaviorists  can 
claim  much  for  their  contention  that  emotion  (like  everything  else 
psychical)  reduces  to  behavior.  Probably  the  "rushing,  excitement, 
or  burning"  felt  by  the  Greek,  as  his  Ovjids  was  in  his  chest,  and 
hence  the  Homeric  placement  of  dvfids.  Moreover,  animxis  and  spir- 
itus  suggest  the  same  thoracic  placement  of  emotion.  Xenophon 
and  others  use  afibymia,  6.dvixla,  for  want  of  heart,  faint-heartedness, 
despondency. 

Protbymic  procedures,  then,  are  enheartening,  inspiriting  meas- 
ures. Despite  the  Socratic  and  intellectualizing  tendency  of  Xeno- 
phon, his  morale  measures  are  within  the  domain  of  emotions 
and  will.  Whether  they  belong  more  amongst  emotion-producing 
procedures  or  amongst  volition-producing  procedures  is  a  special 
question  that  can  hardly  be  answered  before  the  whole  big  question 
of  behaviorism  gets  an  answer. 

The  tabulation  of  protbymic  factors,  above  attempted,  suggests 
a  prehminary  answer  to  the  question  whether  morale  measures 
are  more  emotional  or  more  volitional.  This  preliminary  answer  is 
that  an  itemized  hst  of  such  measures  places  more  of  them  on  the 
will  side  than  on  the  feeling  side. 

Whether  the  morale  or  protbymiay  duly  produced  according  to 
Xenophon,  is  more  of  an  emotional  or  more  of  a  voHtional  state,  it 
seems  clear  that  the  technique  of  the  production  of  this  protbymic 
status  is  a  technique  via  the  will.  The  roots  of  the  terms  that  figure 
most  prominently  in  Xenophon's  account  have  reference  to  move- 
ment in  some  form  {Bvixbs  from  ^uoj,  rush:  pCoyit),  pcoo/xai,  to  dart, 
robur;  nhos,  root  MA,  yearning,  excitement;  <nrev8eLv,  related  to 
speed;  dappos,  related  to  (fare).  Other  considerations  deal  with  equally 
behavioristic  matters,  such  as  war-cries,  singing,  and  good  cheer 
{TrapaKeKevafjLds) . 


794  MORALE-CONCEPT  IN  "CYROPEDIA" 

I  think  it  safe  to  conclude,  therefore,  that  the  indications  from 
Xenophon  are  that  morale  in  his  sense  (or  protbymiat  if  we  may 
generalize  from  a  favorite  term  of  Xenophon)  is  in  the  making 
largely  a  volitional  affair,  an  affair  of  behavior. 

I  call  attention  to  the  prominence  of  behavior  related  witb  tbe 
chest  {dvfidSf  war-cries,  etc.)  as  connected  with  prothymia.  Frederick 
the  Great  in  "Les  Matinees  Royales"  (pp.  29-32)  contributes  a 
morale-engendering  or  protbymic  principle  that  brings  out  this 
point  re  the  chest:  at  least  so  I  interpret  a  story  Frederick  the 
Great  told  his  nephew.  After  telling  the  "dear  nephew"  about 
riveting  the  attention  of  Europe  on  his  own  skill  in  the  art  of  war, 
he  goes  on  to  say, 

"I  turned  the  head  of  all  the  Powers.  Everyone  considered  himself 
lost,  if  he  could  not  move  arms,  feet,  and  bead  in  the  Prussian  style.  All  my 
soldiers  came  to  think  that  they  were  twice  tbe  men  they  bad  been  before 
when  they  saw  that  they  were  everywhere  aped." 

The  italics  are  not  Frederick's.  Note  that  the  soldiers  of  Frederick 
felt  that  they  were  twice  the  men  they  had  been  before:  is  not  this 
largely  a  matter  of  felt  chest-expansion,  a  feeling  of  thoracic 
lightness  and  power  of  expansion,  a  power  of  inspiration,  aspiration, 
spirit,  afflatus?  But,  as  for  the  rest  of  Europe,  all  they  did  (in  the 
words  of  the  princely  criminal)  was  to  move  arms,  feet,  and  head 
in  the  Prussian  style.  They  arrived  at  rhythmic  imitations  of  the 
movements  of  the  limbs  and  a  perfect  copy  of  the  Prussian  carriage 
of  the  head.  But  the  Prussian  still  felt  himself  twice  the  man. 

Conclusions,  i.  The  material  in  Xenophon's  "Cyropedia"  indi- 
cates the  probable  great  value  of  a  historical  study  of  the  morale- 
concept,  a  study  that  might  enliven  the  ethics  of  the  day. 

2.  The  itemizing  of  morale-measures  found  in  the  "Cyropedia" 
indicates  the  probable  success  of  a  behavioristic  version  of  a  large 
part  of  morale  as  the  Greeks  saw  it. 

3.  In  particular,  the  roots  of  most  of  the  words  employed  in 
Xenophon's  morale-description  are  roots  having  to  do  with  move- 
ment and  speed  (rather  than  with  mere  strength  statistically 
taken),  and  having  little  to  do  with  mere  feelings. 

4.  In  particular,  also,  many  of  the  words  indicate  the  thoracic 
seat  of  the  motions  engaged  (e.g.,  the  early  localization  of  Ovfjibs, 


MORALE-CONCEPT  IN  "CYROPEDIA"  795 

animus,  strong  feeling  and  passion,  derived  probably  from  ^6a), 
rush)  rather  than  a  seat  in  the  head  or  in  the  muscular  system  at 
large:  i.e.,  morale  of  Xenophon's  description  is  more  a  matter  of 
heart  than  of  brawn  or  of  head,  but  "heart"  gets  a  behavioristic 
accounting  rather  than  one  in  terms  of  felt  emotion. 

5.  The  morale  of  Xenophon's  day,  or  at  least  the  morale  of  his 
account  in  the  "Cyropedia,"  is  plainly  far  from  a  complete  story 
of  morale  in  the  modern  sense,  especially  the  morale  developments 
in  armies  and  nations  subsequent  to  the  French  Revolution. 

6.  The  term  protbymia  is  indicated  for  the  morale  situation  as 
depicted  by  Xenophon.  This  term  has  several  advantages: 

(a)  The  term  is  a  leading  term  in  Xenophon's  list. 

(6)  The  root  word  dviJ,6s  has  deep-lying  hints  of  motion  in  it, 
as  well  as  general  usage  in  compounds  suggesting  "heart"  in  a 
figurative  sense;  and  the  prefix  irpo-  has  suitable  intimations  of 
pushing  forward  in  space. 

(c)  Modern  psychiatry  has  come  to  use  the  theme  -tbymia  in 
many  compounds  describing  variants  of  emotion  (e.g.,  bypertbymia, 
paratbymia). 

(d)  The  term  protbymia  is  euphonious  and  readily  suggests 
variants,  e.g.,  protbymic  (adjective  to  be  used  of  morale  procedures) 
and  protbymics  (substantive  for  the  art  of  morale,  or  for  our  accumu- 
lation of  facts  concerning  morale). 


THE  MEDICAL  HISTORY  OF  TWO  CRUSADES 
By  James  J.  Walsh,  M.D.,  New  York 

PERHAPS  nothing  would  seem  more  improbable,  not  to  say 
quite  impossible,  to  most  of  the  men  of  our  time  than  the  idea 
that  there  could  be  any  even  far-fetched  comparison  between 
the  medical  history  of  the  Great  War  through  which  the  world  has 
just  passed  and  that  of  the  wars  of  old  times.  Above  all,  it  would 
seem  as  though  there  could  be  no  possible  medico-surgical  com- 
parison between  our  world  war,  "the  crusade  to  make  the  world 
safe  for  democracy,"  and  those  earlier  Crusades  of  the  later  Middle 
Ages  some  eight  centuries  ago,  when  Europe  poured  out  her  men 
so  lavishly  in  order  that  the  Holy  Land  might  be  made  safe  for  all 
those  who  wished  to  seek  inspiration  for  life  there  where  His  foot- 
steps had  hallowed  earth.  Yet  the  surprising  thing  is  that  recent 
developments  in  the  history  of  medicine  have  made  the  medical, 
and  strangest  of  all,  as  it  must  seem,  the  surgical  history  of  these  two 
periods  take  on  much  more  of  similarity  than  could  possibly  have 
been  credited,  only  that  the  actual  documents  with  the  details  of 
the  story  of  that  earlier  period  are  now  before  us. 

The  most  incredible  feature  of  the  old  time  Crusader  history  is 
the  wonderful  chapter  which  gives  the  details  of  the  surgical  develop- 
ment that  took  place  at  that  time.  Any  surgery  really  worthy  of  the 
name  is  commonly  supposed  to  be  an  evolution  of  the  last  genera- 
tion. Before  that,  surgery  confined  itself  almost  entirely  to  emer- 
gency surgical  intervention  or  to  the  saving  or  prolongation  of  Ufe 
when  there  was  otherwise  no  hope  for  the  patient.  Lives  were  oc- 
casionally saved  by  briUiant  surgical  interference,  especially  in  the 
tying  of  large  arteries,  but  except  for  amputations,  expectant  treat- 
ment was  the  rule,  surgeons  naturally  dreading  the  occurrence  of 
infections  and  the  almost  inevitably  prolonged  convalescence,  to 
say  nothing  of  the  frequent  fatalities  which  followed  operations. 

In  complete  contradiction  to  this  idea,  however,  we  have  the 
surgical  text  book  of  Theodoric,  who  wrote  down  for  us  the  details 

796 


THE  MEDICAL  HISTORY  OF  TWO  CRUSADES     797 

of  the  surgical  practice  of  his  father,  Ugo  or  Hugh  of  Lucca,  as  he 
was  called,  who  was  a  surgeon  on  one  of  the  Crusades  and  took 
advantage  of  the  experience  thus  attained  to  develop  surgery  to  a 
marvelous  degree,  along  exactly  the  same  lines  that  it  has  followed 
in  its  recent  evolution.  The  most  surprising  things  Theodoric  tells 
us  are  with  regard  to  the  variety  of  the  surgical  operations  per- 
formed by  his  father,  and  the  extent  to  which  he  went  in  surgical 
intervention  for  the  saving  of  life  and  suffering.  Ugo  operated  for 
tumor  and  for  abscess  within  the  cranial  cavity,  opened  the  thorax 
for  pus  as  well  as  fluid,  and  operated  within  the  abdomen  on  a  great 
many  diff'erent  conditions.  He,  or  some  of  his  contemporaries,  per- 
formed operations  for  the  radical  cure  of  hernia  with  the  patient  in 
an  exaggerated  Trendelenburg  position,  head  down  on  a  board 
leaning  against  a  wall,  in  order  that  the  loops  of  intestines  might 
fall  away  from  the  site  of  operation. 

Ugo's  operations  within  the  abdomen,  however,  are  the  most 
interesting  for  us,  for  he  insisted  that  whenever  the  intestines  were 
wounded  they  must  be  sewed  up,  or  else  the  patients  would  die. 
He  seems  to  have  invented  a  series  of  special  instruments  and  to 
have  elaborated  a  detailed  technic  in  order  to  repair  intestinal 
wounds.  Whenever  the  wound  in  the  intestine  was  large,  he  sug- 
gested separating  the  bowel  into  two  parts  and  placing  a  hollow 
metal  cylinder  within  the  lumen.  Over  this  the  severed  intestinal 
ends  were  brought  together  and  sewed  "with  fine  thread  made  from 
the  intestines  of  animals"  or  "with  fine  silk."  The  metal  cylinder 
used  for  the  purpose,  he  suggested,  might  be  obtained  from  the 
sackbut,  a  muscial  instrument  of  the  time,  from  which  evidently 
certain  parts  were  readily  removable.^ 

Theodoric  tells  us  that  the  lives  of  a  number  of  patients  had  been 
saved  in  this  way,  and  that  the  metal  tube  would  pass  out  after  a 
while,  but  would  usually  not  be  displaced  from  its  position  until 
after  such  agglutination  of  the  intestinal  ends  had  taken  place  as 
would  prevent  leakage  from  the  bowels.  Some  generations  later, 
dissatisfied  with  the  use  of  the  metal  tube  as  an  adjunct,  the  Brancas 
in  Italy,  father  and  son,  proposed  the  use  of  the  trachea  of  an  animal 
as  an  adjuvant  to  maintain  the  patulousness  of  the  intestines  until 
such  healthy  healing  took  place  as  would  prevent  leakage.  Mani- 

*  See  Gurit,  "Geschichte  der  Chirurgie." 


798     THE  MEDICAL  HISTORY  OF  TWO  CRUSADES 

festly,  they  had  experienced  delays  and  complications  in  the  pas- 
sage of  the  metal  tube,  and  they  suggested  that  this  animal  tissue, 
the  cartilage  of  the  trachea,  would  be  gradually  absorbed,  but  not 
until  it  had  accomplished  the  purpose  of  keeping  the  intestinal 
lumen  open  until  safe  healing  had  taken  place.  It  is  easy  to  under- 
stand that  men  who  were  doing  things  of  this  kind  were  quite  capable 
of  surgical  intervention  for  other  conditions  within  the  abdomen, 
and  that  they  must  have  been  rather  successful,  since  the  record  of 
their  work  remains  some  seven  centuries  later. 

Of  course  it  would  have  been  quite  impossible  for  surgeons  to 
have  accomplished  successfully  such  extensive  operative  measures 
without  the  use  of  some  form  of  antiseptic.  At  the  beginning  of  the 
late  war,  it  is  said  that  over  70  per  cent  of  the  wounds  received  in 
the  trenches  were  seriously  infected.  Army  medical  departments 
had  anticipated  aseptic  rather  than  antiseptic  surgery,  and  were 
utterly  unprepared  for  this  unlooked-for  state  of  affairs,  and  so 
their  work  for  a  time  broke  down  rather  seriously.  Then  there  came 
the  development  of  antiseptic  methods,  and  the  situation  was 
saved,  so  that  only  a  very  small  percentage  of  those  who  lived  to 
reach  the  base  hospitals  died  from  their  wounds.  The  methods  had 
to  be  elaborated  during  the  war,  however;  but,  thanks  to  co- 
operation, they  were  soon  so  perfected  that  a  great  deal  of  suffering 
and  mortality  was  saved.  The  immense  call  made  on  the  sympa- 
thy and  intellectual  resources  of  those  who  saw  all  the  suffering 
that  there  was,  had  almost  inevitably  to  meet  an  adequate  re- 
sponse. 

Similar  conditions  worked  a  like  miracle  of  human  resourceful- 
ness in  the  Crusader  times.  They,  too,  learned  the  precious  lesson, 
probably  not  until  after  many  lives  had  been  lost,  that  certain 
modes  of  dressing  wounds  saved  complications  and  sequelae.  They 
found  empirically  that  strong  wine  was  particularly  likely  to  be 
followed  by  prompt  healing.  They  soaked  dressings  of  flax  or  linen 
in  this  fluid,  covered  the  wound  with  them,  and,  placing  other 
dressings  above,  bound  up  the  parts.  As  the  strong  wine  evaporated 
after  a  time,  they  called  this  the  "dry  dressing,"  and  Theodoric 
was  very  proud  of  the  fact  that  his  father  used  it  so  successfully. 
He  boasted  of  his  getting  "union  by  first  intention"  with  it,  and 
the  very  expression  per  primam  intentionem,  is  a  medieval  Latin 


THE  MEDICAL  HISTORY  OF  TWO  CRUSADES     799 

phrase  which  has  no  meaning  in  the  modern  languages  when  trans- 
lated literally  as  "first  intention,"  except  what  it  borrows  from  the 
old  Latin. 

Theodoric  tells  that  his  father  not  only  cured  wounds  by  this 
means,  but  he  made  them  "heal  solidly  as  before,"  and  succeeded 
in  obtaining  "very  beautiful  (pulcberrimas)  cicatrices  without  any 
ointment."  These  last  words  are  a  reference  to  the  fact  that  many 
surgeons  thought  it  necessary  to  make  unguent  applications  of 
various  kinds  in  order  to  bring  about  healing,  yet  they  really  only 
hindered  union. 

It  is  no  wonder  that  Theodoric  understood  perfectly  clearly 
the  question  of  the  formation  of  pus,  and  expressed  himself  very 
decisively  against  the  teaching  which  maintained  that  pus  was 
inevitable,  and  that  the  one  hope  of  the  surgeon  must  be  to  encour 
age  the  formation  of  a  kind  of  pus  that  would  do  as  little  harm  as 
possible  to  the  patient.  There  were  evidently  advocates  of  "  laudable 
pus,"  or  something  of  that  kind,  at  that  time,  and  some  of  the  older 
teachers  had  laid  down  the  doctrine  which,  unfortunately,  in  spite 
of  Theodoric's  explanation  of  his  father's  practice,  came  to  be 
accepted  as  the  standard  teaching  for  centuries,  even  to  our  own 
time.  Neuberger,  the  German  historian  of  medicine,  quotes  Theo- 
doric as  saying:  "For  it  is  not  necessary — as  Roger  and  Roland 
have  said,  as  most  of  their  disciples  teach,  and  as  almost  all  modern 
(italics  ours  to  call  attention  to  the  use  of  the  word  'modem*  in 
the  thirteenth  century)  surgeons  practice — to  favor  the  generation 
of  pus  in  wounds.  The  doctrine  is  a  very  great  error.  To  follow  such 
teachings  is  simply  to  put  an  obstacle  in  the  way  of  nature's  efforts, 
to  prolong  the  diseased  action,  and  to  prohibit  the  agglutination 
and  final  consolidation  of  the  wound." 

After  reading  this,  it  is  much  easier  to  understand  some  of  the 
details  of  this  Crusader  surgeon's  technic,  as  given  in  his  son's 
text  book.  It  is  summarized  in  Gurlt's  "Geschichte  der  Chirurgie" 
(Berlin,  1898).  He  insisted  on  special  care  in  bringing  together  the 
edges  of  wounds,  both  deep  and  superficial  sutures  being  employed 
if  necessary.  He  declared  against  the  common  teaching  of  the  time 
as  to  the  use  of  a  wick  of  absorbent  material  for  draining.  His  reason 
was  that  this  prolonged  healing,  encouraged  uncleanliness,  and 
hampered  repair  and  cicatrization.  He  warned  against  the  use  of 


8oo     THE  MEDICAL  HISTORY  OF  TWO  CRUSADES 

salves  in  wounds  of  the  scalp  particularly,  and  called  attention  to 
the  possibilities  of  serious  complications  here.  The  hair  should  be 
shaved  and  a  compress  soaked  in  hot  wine  employed  to  bring  the 
edges  together,  sutures  being  dangerous.  He  had  seen  many  patients 
recover  completely  from  injuries  to  the  brain  even  after  the  loss  of 
some  brain  substance,  though  many  surgeons  had  declared  that 
event  surely  fatal.  He  had  seen  one  case  where  one  of  the  cells  of 
the  brain  (probably  a  ventricle,  as  Gurit  suggests)  had  been  com- 
pletely evacuated,  and  yet  the  patient  recovered  perfectly — an 
anticipation  of  our  famous  tamping-iron  case.  He  describes  in  detail 
how  tonsils  should  be  removed,  the  uvula  clipped,  pharyngeal  ab- 
scesses opened,  and  nasal  polyps  removed.  He  dared  even  to  suggest 
radical  operations  for  goiter,  though  he  warned  of  the  danger  from 
hemorrhage,  and  that,  therefore,  the  operation  must  be  undertaken 
only  with  the  greatest  care  and  foresight. 

Almost  needless  to  say,  it  would  have  been  quite  impossible 
to  have  done  such  extensive  deliberate  operating  as  is  thus  suggested 
on  head,  neck,  and  abdomen  without  anesthetics.  The  greatest 
surprise  of  all  is  to  find  that  they  were  using  anesthetics  very 
commonly  at  this  time.  When  the  English  poet  Middleton,  early 
in  the  seventeenth  century,  wrote  of  "the  pities  of  old  surgeons  who 
put  their  patients  to  sleep  before  they  cut  them,"  his  readers  of 
the  generations  before  ours  scarcely  knew  what  to  make  of  Middle- 
ton's  suggestion  of  a  former  anticipation  of  what  seems  to  us  our 
anesthesia.  The  old  Crusader  surgeons,  and  among  them  particu- 
larly Ugo  of  Lucca,  used  a  combination  of  mandragora,  opium,  wild 
lettuce,  and  hyoscyamus  for  anesthetic  purposes.  Tinctures  of  these 
pharmacals  were  employed  and  a  sponge  saturated  with  them.  The 
technic  of  anesthesia  was  to  allow  this  to  dry  in  the  sun,  and  then, 
having  placed  it  in  boiling  water,  to  allow  the  patient  who  was  to  be 
operated  on  to  inhale  the  steam  from  it.  The  use  of  a  sponge  in  this 
way  and  the  obtaining  of  narcosis  by  inhalation  is  particularly 
interesting.  There  is  no  doubt  at  all  that  these  old  surgeons  thus 
secured  thoroughly  efficient  anesthesia,  though,  almost  needless  to 
say,  their  anesthetics  were  neither  so  safe  nor  so  certain  nor  so 
reliable  as  ours. 

No  wonder  that  surgeons  who  had  solved  thd  hardest  surgical 
problems  so  successfully  as  all  this  indicates  could  give  explicit 


THE  MEDICAL  HISTORY  OF  TWO  CRUSADES     80 1 

directions  for  the  bandaging  of  a  compound  fracture  as  simply  as 
possible,  with  a  compress  over  the  wound  moistened  in  warm  wine, 
the  dressing  not  to  be  touched  for  ten  days  unless  some  complication 
was  manifestly  developing.  No  albumin  bandage  was  to  be  used  in 
compound  fractures,  and  lard  and  honey  salves  must  be  avoided. 
No  wonder,  either,  that  they  warn  of  the  possibility  of  capillary 
fractures  of  the  skull,  or  of  fracture  by  contrecoup,  that  is,  on  the 
opposite  side,  from  the  blow  or  injury.  Manifestly,  they  were  men 
deeply  intent  on  their  work,  making  careful  clinical  observations 
and  not  dependent  at  all  on  theory  or  tradition  unless  it  was  sup- 
pK)rted  by  their  own  experience. 

Such  good  surgery  could  not  have  been  accomplished  except  in 
well-conducted,  thoroughly  organized,  and  faithfully  maintained 
hospitals.  We  all  know  now  that  for  good  surgery,  good  nursing  and 
good  hospitals  are  absolutely  indispensable  co-ordinate  conditions, 
and  that  before  Lister's  time  the  difficulty  of  doing  good  surgery 
was  greatly  increased,  not  only  by  the  lack  of  knowledge  of  the 
principles  of  antisepsis,  but  also  by  the  extremely  unfortunate  con- 
ditions of  the  hospitals  of  that  time.  The  nurses  were  often  "ten- 
day  women,"  usually  of  no  character,  always  looked  upon  as  scarcely 
more  than  menials,  with  only  the  most  meager  knowledge  of  how  to 
care  for  medical  patients,  and  knowing  next  to  nothing  about  the 
care  of  surgical  patients. 

In  this,  then,  was  the  second  significant  anticipation  of  our  mod- 
ern developments,  for  quite  literally  they  must  have  had  good 
hospitals  and  good  nurses.  This  is  actually  what  is  found  in  the 
medical  history  of  the  time,  for  the  hospitals  very  soon  after  the 
beginning  of  the  old  Crusading  period  had  become  beautiful  build- 
ings, and  the  care  of  the  patients  in  them  was  carried  to  a  point  of 
refinement  that  has  made  them  examples  in  history.  We  have  the 
story  of  the  organization  of  a  series  of  nursing  orders,  both  men  and 
women,  whose  one  purpose  was  the  care  of  wounded  and  ailing 
Crusaders.  The  famous  nursing  order  of  St.  John  of  Jerusalem,  whose 
original  purpose  was  solely  to  bring  in  the  wounded  and  to  serve 
in  the  hospitals,  and  who  came  as  a  consequence  to  be  called  the 
Hospitallers,  is  a  typical  example. 

According  to  the  letter  of  a  pilgrim,  about  the  middle  of  the 
twelfth  century,  their  hospital  of  St.  John  of  Jerusalem  was  capable 


8o2     THE  MEDICAL  HISTORY  OF  TWO  CRUSADES 

of  taking  care  of  2000  patients.^  This  would  give  one  an  idea  of  how 
extensive  were  the  hospital  arrangements  of  the  time.  The  Ladies 
of  St.  Mary  Magdalen  represented  the  feminine  branch  of  the  Hos- 
pitallers, and  their  hospital,  according  to  tradition,  was  scarcely 
less  extensive.  Besides,  there  was  a  nursing  order  of  Lazaristsaswell 
as  that  of  the  Templars,  whose  original  hospital  was  on  the  site  of 
the  Temple  of  Solomon,  hence  their  name.  Both  the  Knights  of  St. 
John  and  the  Templars  afterwards  found  themselves  compelled  to 
establish  a  fighting  branch  of  their  orders  in  order  to  defend  their 
wounded  while  they  were  bringing  them  in,  and  to  care  for  the 
pilgrims  who  were  liable  to  attack.  Our  Red  Cross  met  with  the 
same  dangers  in  our  time  in  spite  of  supposed  progress  in  humanity 
since.  These  military  developments  did  not  come,  however,  until 
well  on  in  the  thirteenth  century,  and  in  the  meantime,  the  origi- 
nal purpose  of  a  nursing  order  was  the  sole  one  and  was  fulfilled 
admirably. 

Two  things  they  were  famous  for — first,  the  abundance  of  food 
provided  for  patients,  and  secondly,  the  readiness  to  obtain  any- 
thing for  those  who  were  suffering  that  could  possibly  do  them  any 
good.  Theodoric  has  told  us  that  his  father  considered  nutrition 
one  of  the  most  important  adjuvants  for  the  success  of  the  surgeon's 
work.  He  adds  the  weight  of  his  own  experience  in  this  regard,  and 
as  at  the  time  he  wrote  he  was  a  man  of  some  sixty  years  of  age, 
who  had  had  much  practical  experience,  his  opinion  is  of  great 
significance.  He  said : 

"Since,  therefore,  nature  herself  cannot  bring  about  the  manufacture 
of  good  blood  without  proper  nutriment,  nothing  avails  more  in  the  healing 
of  small  as  well  as  great  wounds  as  the  care  of  the  nutrition  of  the  patient. 
The  physician  must,  above  all,  not  be  ignorant  of  the  kind  of  food  materials 
that  generate  good  chyme  and  good  blood.  Out  of  such  materials  the 
wounded  man  must  be  fed,  in  order  that  a  suitable  diet  shall  bring  about  a 
restoration  of  health  and  the  renascence  of  the  flesh  and  the  restoration 
of  the  continuity  of  the  wound." 

These  hospitals  were  richly  endowed,  for  the  great  heart  of  hu- 
manity poured  itself  out  for  these  early  Crusaders  quite  as  gener- 
ously as  for  the  Crusaders  of  our  own  time.  The  Hospitallers  of  St. 
John  of  Jerusalem  and  the  Sisters  of  St.  Mary  Magdalen  came  to 

*  See  article,  "Hospitals,"  Catholic  Encyclopedia. 


THE  MEDICAL  HISTORY  OF  TWO  CRUSADES     803 

own  properties  in  many  parts  of  Europe.  Many  of  these  donated 
properties,  especially  along  the  seacoast  of  southern  Italy,  France, 
and  Spain,  came  to  be  used  as  what  we  would  call  sanatoria  for  the 
care  of  convalescent  soldiers  from  the  wars  in  the  East,  under  such 
circumstances  as  would  best  enable  them  to  recover  their  health 
after  the  severe  ills  and  wounds  to  which  they  had  been  subjected. 
To  a  great  extent  these  houses  of  recuperation  were  in  charge  of  the 
nursing  sisters  of  St.  Mary  Magdalen,  whose  great  hospital  in 
Jerusalem  was,  as  we  have  said,  almost  as  famous  as  that  of  the 
Hospitallers  themselves,  and  who  took  the  occasion  of  these  dona- 
tions of  properties  to  establish  branch  houses  in  many  parts  of  the 
world. 

By  another  curious  anticipation  of  the  modern  time,  these  houses 
after  the  Crusades  came  to  be  looked  upon  as  centers  upon  which 
calls  could  be  made  in  time  of  flood  and  famine  and  plague  and  war. 
The  development  was  indeed  very  like  that  of  the  Red  Cross,  and 
came  to  be  a  great  humanitarian  resource  at  critical  times  in  a 
very  wonderful  way.^ 

In  a  word,  here  are  rather  striking  anticipations  in  that  older 
time  of  most  of  the  developments  that  would,  at  first  thought,  at 
least,  seem  so  surely  novel  in  our  time.  There  was  a  magnificent 
evolution  of  surgery  in  war  time  which  proved  of  fine  service  for 
civil  surgery  during  and  after  the  war.  Anesthesia  and  antisepsis 
were  anticipated  in  the  midst  of  the  great  needs  of  the  time.  With 
these,  surgery  developed  to  an  almost  incredible  ingenuity  of  detail 
in  technic  and  of  power  to  save  life  and  suff'ering.  Hospitals  had  to 
be  organized  well  to  take  care  of  these  surgical  patients,  and  nursing 
was  established  on  a  new  and  finely  efficient  footing.  Through  the 
channels  of  charity  there  flowed,  quite  as  in  our  time,  the  off"erings 
that  made  all  this  organization  of  welfare  work  for  the  Crusaders 
possible,  and  that  organization  carried  over  into  the  time  of  peace 
after  the  Crusades  proved  to  be  the  best  solution  of  the  civil  prob- 
lems of  suff'ering  among  mankind,  which  had  before  that  nearly 
always  swamped  the  community  in  which  they  occurred,  no  matter 
how  much  of  good  will  there  was. 

A  word  in  conclusion  may  serve  to  point  out  another  similarity 
between  the  Crusading  times  and  our  own,  which  we  have  every 

•  Nutting  and  Dock,  "History  of  Nursing." 


8o4     THE  MEDICAL  HISTORY  OF  TWO  CRUSADES 

right  to  hope  will  be  fulfilled.  A  great  many  people  have  been  inclined 
to  be  pessimistic  as  to  the  immediate  future  of  civilization  after 
the  war,  because  so  many  men  in  the  flower  of  their  lives  have  been 
cut  off  by  war's  destructiveness  that  surely  the  next  two  or  three 
generations  will  be  seriously  hampered  in  their  efforts  towards 
progress.  The  answer  of  a  French  surgeon  deserves  to  be  recalled 
in  this  regard.  When  it  was  remarked  to  him  that  France  was 
losing  an  immense  number  of  men,  he  said,  "Oh,  yes,  we  are  losing 
enormously  in  numbers,  but  for  every  man  we  lose  we  are  making 
two  men."  His  idea  was  that  it  is  the  spirit  of  man  and  not  his 
numerical  quantity  that  counts  for  human  achievement.  Men  who 
in  the  words  of  a  young  English  poet  who  died  during  the  war,  "have 
had  their  souls  touched  by  flame  in  the  trenches,"  will  surely  have 
a  new  power  to  do  things  after  they  come  back  from  the  war.  As 
one  of  our  great  captains  of  industry,  "a  dollar-a-year"  man  for 
the  Government  during  the  war,  said,  "What  we  must  have  now  is 
not  reconstruction,  but  renovation.  We  must  not  merely  rebuild 
the  old  world,  but  renew  the  very  face  of  the  earth." 

What  happened  after  the  medieval  crusades  is  very  interesting 
in  this  regard.  Europe  lost  several  millions  of  men  during  the  twelfth 
century  when  she  could  apparently  ill  aff'ord  them  from  her  scanty 
population.  It  might  easily  be  expected  that  this  would  cripple  the 
power  of  achievement  for  several  centuries.  As  a  matter  of  fact, 
it  had  just  the  opposite  eff'ect,  and  the  crusading  spirit  touched  the 
souls  of  men  so  deeply  that  there  are  not  a  few  of  us  who  are  inclined 
to  speak  of  "The  Thirteenth  as  the  Greatest  of  Centuries."  Mere 
material  losses  do  not  count  if  only  the  spirit  of  man  is  aroused  from 
over-attention  to  sordid,  material  affairs,  and  stimulated  to  do  work 
that  is  significant  for  the  mind  and  the  heart  and  the  soul  of  hu- 
manity. This  deep  touching  of  the  human  heart  may  very  well 
prove,  after  our  modern  crusade,  as  after  those  first  Crusades,  to 
be  the  initiative  of  a  magnificent  period  of  accomplishment. 

BIBLIOGRAPHY 

"Cyrurgia  Guidonis  de  Cauliaco;  Cyrurgia  Bruni,  Teodorici  Rolandi, 
Lanfranci,  Rogerii  Bertapaliae,  etc."  270  ff.  folio  Venetiis  imp.  Andreas 
Torresani  de  Asula,  1499. 

Gurit,  "Geschichte  d.  Chirurgie,"  Berlin,  1898. 


THE  MEDICAL  HISTORY  OF  TWO  CRUSADES     805 

Neuburger,  "Geschichte  d.  Medizin,"  Stuttgart,  1908. 

Buck,   "The   Growth   of  Medicine   from   the    Earliest  Times  to  about 

1800,"  Yale  University  Press,  New  Haven,  19 17. 
Lallemand,  "Histoire  de  la  Charite,"  Paris,  1902-10. 
Hoeser,  "Geschichte  christ.  Krankenpflege,"  Berlin,  1857. 
Nutting  and  Dock,  "History  of  Nursing,"  New  York,  1907. 
Walsh,  "The  Thirteenth,  Greatest  of  Centuries,"  New  York,  1908. 


A  SOUVENIR  OF  THE  MACARTNEY  MUSEUM 
By  J.  Collins  Warren,  M.D.,  Boston,  Mass. 

IN  a  recess  of  an  old  family  cabinet  there  has  reposed  for  over 
three-quarters  of  a  century  a  portion  of  tanned  human  skin. 
Tradition  had  it  that  the  former  possessor  was  none  other  than 
Madame  du  Barry,  one  of  the  celebrities  of  the  court  of  Louis  XV., 
and  that  it  came  from  the  breast  of  that  famous  beauty.  In  one 
corner  there  is  a  perforation  suggesting  the  site  of  the  mammary 
nipple,  which  lends  color  to  this  claim.  The  responsibility  for  this 
story  is  not  quite  clear,  but  the  death  of  the  former  owner  of 
the  specimen  in  1867  has  left  this  version  somewhat  shrouded  in 
mystery. 

On  the  inner  surface  of  the  specimen  is  a  faded  inscription,  which 
with  some  difficulty  may  be  deciphered  as  follows: 

"A  portion  of  the  skin  of  Madame  Barre,  a  heroine  of  the  French 
Revolution  who  left  her  body  to  be  dissected  (18 10)  and  to  be 
given  the  surgeon  to  defray  expenses.  Presented  to  J.  M.  Warren 
by  Dr.  Macartney,  Professor  of  Trinity  College,  Dublin." 

The  young  man  to  whom  Macartney  had  given  this  specimen 
was  one  of  a  group  of  American  medical  students  who,  following 
the  fashion  of  that  particular  period,  were  devoting  most  of  their 
time  to  the  Paris  School.  They  were  first  and  foremost  pupils  of 
Louis,  or,  if  surgically  incfined,  of  Dupuytren,  Roux,  and  Civiale, 
but  they  loved  to  visit  the  great  centers  of  medicine  and  surgery 
in  Great  Britain  which  had  been  the  resort  of  their  fathers  at  the 
beginning  of  the  century.  It  was  during  one  of  these  excursions  that 
Dr.  Warren  visited  Dubfin,  a  seat  of  medical  learning,  which  was 
beginning  to  attract  the  attention  of  the  faculties  of  London  and 
Edinburgh.  No  doubt  it  was  largely  due  to  the  rising  fame  of  James 
Macartney  as  a  teacher  of  anatomy  and  surgery  that  the  travefing 
student  felt  that  he  could  not  afford  to  allow  such  an  opportunity 
to  be  neglected. 

806 


A  SOUVENIR  OF  THE  MACARTNEY  MUSEUM     807 

Born  in  Ireland  in  1770,  Macartney's  early  education  was 
largely  interfered  with  by  the  unrest  of  the  times,  but  as  a  medical 
student  in  London  he  was  able  to  pursue  his  studies  under  the 
many  distinguished  teachers  who  were  following  in  the  footsteps 
of  Hunter.  From  the  lectures  of  Abernethy,  Cooper,  Davy,  Haigh- 
ton,  and  others  he  was  able  to  give  his  natural  tastes  and  abilities 
full  play.  The  history  of  his  appointment  as  professor  of  anatomy 
and  chirurgery  in  the  University  of  Dublin,  his  struggle  with  the 
prejudices  and  conservatism  of  his  colleagues,  the  development  of 
the  Dublin  School,  and  the  formation  of  hFs  famous  anatomical 
collection  are  too  well  told  by  another  to  permit  me  to  dwell  upon 
them  here.^ 

At  the  time  of  the  young  medical  student's  visit  to  Dublin, 
Macartney  had  reached  the  height  of  his  career,  and  in  turning  to 
the  letter  of  the  son  to  the  father  for  further  information  about  our 
specimen,  we  find  incidentally  much  to  interest  us  in  the  man 
himself. 

"Dublin,  August  2,  1834 
"My  dear  Father: 

"...  Part  of  another  day  I  devoted  to  the  museum  of  Dr.  Macartney 
at  Trinity  College.  He  made  an  appointment  and  occupied  two  hours  in 
showing  me  the  whole  of  it.  The  preparations  are  many  of  them  very 
fine  and  made  by  himself,  he  giving  the  greater  part  of  his  time  to  the  sole 
object  of  preparing  for  his  lectures  on  anatomy  and  physiology,  of  which 
he  is  professor  in  Trinity  College.  Among  the  curiosities  which  he  has  here 
is  a  paper  signed  by  a  great  number  of  persons,  himself  at  the  head,  for 
giving  their  bodies  after  death  to  be  dissected.  He  has  already  the  skeleton 
of  one  or  two  persons  who  have  given  their  bodies, — one  of  Dr.  O'Connor, 
whose  heart  he  has  burned.  He  preserves  the  ashes  in  a  little  bronze  vase 
on  a  marble  pedestal  with  an  appropriate  inscription.  He  also  has  the  arm 
exposed  with  the  skin  on  in  a  dried  state.  Besides  O'Connor's  body,  Dr. 
Macartney  has  the  skeleton  of  Madame  Barr6,  a  celebrated  Amazon 
under  Robespierre  in  the  French  Revolution  and  a  correspondent  of  Bona- 
parte's. She  left  her  body  and  ten  pounds  to  have  it  dissected  by  the  doctor, 
writing  this  part  of  her  will  with  her  own  hand.  He  has  also  a  portion  of 
her  skin  tanned  quite  as  good  as  shoe-leather,  of  which  he  gave  me  a  piece 
for  your  museum.  He  has  also  the  skeleton  of  a  man  with  many  of  the 

*  "James  Macartney,  M.D.,  St.  Andrews  and  Dublin,  Hon.  LL.D.,  Cambridge, 
F.R.S.,  Professor  of  Anatomy  and  Chirurgery  in  the  University  of  Dublin."  A 
Memoir  by  Alexander  Macalister,  Professor  of  Anatomy,  Cambridge,  1900. 


8o8     A  SOUVENIR  OF  THE  MACARTNEY  MUSEUM 

muscles  of  the  back  completely  ossified,  also  of  the  legs,  and  other  parts  of 
the  body.  All  the  joints  are  in  a  state  of  anchylosis.  The  skeleton  of  an 
Irish  giant  seven  and  a  half  feet  high  is  also  curious. 

"Dr.  Macartney  is  one  of  the  most  eccentric  men  I  have  yet  come 
across,  and  his  conversation  was  very  amusing.  He  seems  to  set  but  little 
value  on  his  wax  preparations,  which  he  keeps  in  a  kind  of  outhouse  in  a 
very  good  state  of  preservation.  A  small  burying-ground  for  the  remains 
of  the  dissected  is  just  behind  the  dissecting  room,  and  over  the  entrance 
a  marble  slab  with  something  like  the  following  inscription:  'Here  lie  the 
bodies  of  those  who  after  their  death  have  honorably  chosen  to  be  of  use 
to  their  fellow  creatures.' 

"  Dr.  Macartney  gave  me  some  good  hints  as  to  making  preparations — 
one  for  the  preservation  of  their  color,  which  is  to  immerse  them,  previous 
to  putting  them  in  spirit,  in  a  solution  of  alum  and  nitrate  of  potash.  Wet 
preparations  may  be  injected  with  this  for  preserving  their  forms,  and 
may  also  be  sufficiently  hardened  to  keep  without  the  aid  of  spirit.  .  .  . 

"J.  M.  Warren." 

It  will  be  seen  at  once  that  the  written  testimony  is  quite  at 
variance  with  the  version  given  at  the  beginning  of  this  article.  In 
order  to  clear  up  its  history  before  giving  the  fragment  of  skin  a 
final  resting  place  in  the  museum  of  the  Harvard  Medical  School, 
information  was  sought  from  Sir  William  Osier,  by  whom  my  letter 
was  referred  to  Professor  Alexander  Macalister.  In  the  preface  to  a 
Memoir  of  James  Macartney,  Macalister  says:  "When  in  after  years 
it  was  my  lot  to  succeed  to  the  Professorship  which  he  had  held  and 
when,  still  later,  I  followed  his  Museum  from  Dublin  to  Cambridge 
and  taught  from  the  specimens  which  his  hands  had  made,  the 
Macartney  teaching  and  the  Macartney  traditions  became  to  me 
realities  of  peculiar  interest."  I  am  therefore  taking  the  liberty  of 
giving  in  full  a  letter  from  Macalister  to  Osier. 

"TORRISDALE,    CAMBRIDGE, 

March  20,  19 16. 

"As  Madame  du  Barr^  (Marie  Jeanne  B^cu)  was  guillotined  in  Paris 
December  7,  1793,  and  was  only  in  England  for  a  short  time  in  1792 
trying  to  sell  her  jewelry,  it  is  obvious  that  the  skeleton  and  story  are 
not  hers. 

"The  Madame  Barre  whose  skeleton  I  have  here  was  at  her  death  an 
old  woman  over  sixty,  a  well-known  Danseuse  of  very  bad  character  in 


A  SOUVENIR  OF  THE  MACARTNEY  MUSEUM     809 

Dublin.  I  believe  it  is  true  that  she  left  her  body  to  Macartney,  but  I 
have  no  documentary  evidence.  She  called  herself  a  French  woman  but  I 
believe  she  was  Irish  and  really  by  name  Barry. 

"Dr.  Warren  is  confusing  two  things.  A  certain  doctor  in  Dublin  (Dr. 
O'Connor)  did  in  his  will  bequeath  his  body  to  Macartney  and  left  him 
ten  pounds  to  pay  expenses  of  dissection.  I  have  the  will. 

"As  Barre  died  in  poverty  I  think  it  much  more  likely  that  she  died 
destitute  and  was  brought  in  by  the  Resurrectionists,  but  there  is  no 
reference  that  I  can  remember  among  Macartney's  papers  to  her.  However 
I  shall  look  again  over  them. 

"P.  S.  There  is  a  life  of  the  real  Comtesse  du  Barre,  by  Douglas, 
published  in  1896,  which  gives  particulars  as  to  her  execution  and  beheadal. 
My  skeleton  was  not  beheaded. " 

From  the  above  it  is  quite  evident  that  the  possessor  of  this 
piece  of  skin  was  a  person  of  the  name  of  Barry  and  of  Irish  birth. 
The  terminal  letter  "y"  in  the  name  cannot,  however,  be  admitted 
as  convincing  evidence  of  nationality.  In  the  Catalogue  General 
de  la  Biblioth^ue  Nationale  the  name  is  entered  with  various 
spellings,  of  which  two  will  suffice. 

"Du  Barry.  Jeanne  Becu.  The  authentic  memoirs  of  the  Comtesse 
de  Barre  (Du  Barry)  by  Sir  Francis  N.,  etc. 

"  Memoire  Authentique  de  Madame  la  Comtesse  du  Barri,  etc. " 

Under  an  engraving  in  the  possession  of  the  writer,  by  Hum- 
phrey, London,  1770,  the  title  is  given  as  Madame  La  Comtesse  du 
Barr^  (the  "y"  having  been  erased  and  replaced  in  ink  by  an  "e" 
with  a  grave  accent). 

But  we  find  in  the  catalogue  referred  to  another  person  of  the 
same  name. 

"  Dubarry  (Anne-Marie-Ther^se-Rabaudy  MontressinVve.)La  cityonne 
condamn6  k  mort  par  le  tribunal  r^volutionaire  de  Toulouse  au  corps 
L6gislatif  (pour  revendiquer  I'hferitage  de  son  mari)." 

In  view  of  the  evidence  here  submitted,  the  claim  of  the  king's 
favorite  to  the  title  of  ownership  may  be  definitely  dismissed. 

It  is,  however,  quite  clear  that  persons  of  the  name  figured  in 
the  French  Revolution,  and  it  seems  highly  probable  that  Ma- 
cartney's Mrs.  Barry  may  have  masqueraded  as  a  "cityonne  Du- 


8io     A  SOUVENIR  OF  THE  MACARTNEY  MUSEUM 

barry,"  either  carried  away  by  revolutionary  fervor  as  a  follower 
of  Robespierre,  or  serving  in  some  capacity  under  Bonaparte,  as  a 
traditional  foe  of  England.  If  she  were  sixty  years  old  at  the  time  of 
her  death  in  1810,  she  would  have  hardly  passed  her  prime  when 
her  namesake  was  beheaded  in  1793,  and  who  knows  that  the 
possessor  of  this  fragment  of  skin  did  not  have  some  thrilling  episode 
of  which  history  tells  us  not? 

Be  that  as  it  may,  the  fact  remains  that  the  old  keepsake  has 
been  shorn  of  most  of  its  historic  prestige,  and  like  Balzac's  "La 
Peau  de  Chagrin"  has  been  shrinking  rapidly  in  importance.  But 
we  cannot  say  that  this  quaint  old  specimen  has  been  preserved  all 
these  years  wholly  in  vain,  for  has  it  not  been  resurrected  to  revive 
in  memory  and  attract  attention  to  the  name  of  a  surgeon  and 
scientist  who  possessed  that  transcendent  quality  for  a  life's  work 
— enthusiasm;  one  who  fought  hard  to  build  up  a  dormant  institu- 
tion, and  who  has  left  behind  traditions  which  the  Dublin  School 
should  prize  as  among  its  most  precious  possessions? 

And  is  not  this  anniversary  an  occasion  on  which  our  thoughts 
should  turn  to  all  that  stands  for  that  which  is  good  and  true,  and 
to  one  who  has  set  us  an  example  of  what  a  member  of  our  pro- 
fession should  try  to  be?  In  this  spirit  I  venture  to  seek  for  this  tale 
of  a  bygone  time  a  place  among  the  contributions  to  the  day  we  all 
delight  to  celebrate. 


INFLUENCE  OF  ENGLISH  MEDICINE  UPON  AMERI- 
CAN MEDICINE  IN  ITS  FORMATIVE  PERIOD.* 

By  William  H.  Welch,  M.D.,  LL.D. 

IMPORTANT  as  have  been  the  impulses  derived  from  other 
sources,  kinship,  community  of  language,  and  intercourse  have 
combined  to  render  the  influences  coming  from  England  and 
Scotland  the  dominant  ones  in  the  development  of  American 
medicine.  This  statement  is  particularly  applicable  to  the  colonial 
period  and  the  first  half  century  of  the  independence  of  the  United 
States. 

After  this  formative  period  medicine  in  America  assumed  a  more 
independent  character.  In  the  thirties  and  forties  of  the  last  century 
it  received  a  great  and  beneficial  impulse  from  France,  as  has  been 
set  forth  so  admirably  by  Osier  in  his  charming  paper  on  the  Ameri- 
can pupils  of  Louis.  Still  later  from  the  seventies  onward  the  greatest 
stimulus  came  from  Germany,  whither  flocked  a  multitude  of  as- 
piring American  students.  This  influence  was  marked  especially  by 
the  development  of  pathology,  bacteriology,  and  chemistry  and  by 
the  establishment  of  laboratories.  These  later  foreign  influences, 
important  as  they  were,  were  exerted  upon  a  profession  and  a 
medical  art  already  established  which  was  predominantly  English 
and  Scottish  in  origin  and  character. 

The  meager  body  of  medical  knowledge  brought  from  England 
and  Scotland  by  Thomas  Wotton  and  Samuel  Fuller  and  the  little 
band  of  their  successors  in  the  seventeenth  century  was  considerably 
increased  by  immigrant  physicians  and  returning  students,  by  impor- 
tation of  books,  and  by  correspondence  in  the  following  century.  It 
was  transmitted  mainly  by  the  apprenticeship  system.  That  the' 

*  As  this  paper  has  been  written  up>on  a  steamship  crossing  to  France,  without 
access  to  books  or  notes,  it  has  not  been  possible  to  insert  references. 

8ii 


8i2  ENGLISH   AND   AMERICAN   MEDICINE 

spirit  of  inquiry  was  not  absent  is  shown  by  the  additions  to  the 
indigenous  materia  medica,  some  of  which  have  retained  a  per- 
manent place,  and  by  the  introduction  by  Cotton  Mather  and 
Labdiel  Boylston  in  Boston  of  the  practice  of  inoculation  against 
smallpox  almost  simultaneously  with  its  introduction  in  England, 
but  quite  independently,  and  with  a  skill  and  success  equal  to  that 
attained  elsewhere.  The  eighteenth-century  story  of  inoculation 
has  much  the  same  interest  and  runs  much  the  same  course  in 
America  as  in  England. 

Before  the  end  of  the  eighteenth  century  substantial  contribu- 
tions had  been  made  to  the  knowledge,  prevention,  or  treatment  of 
the  three  great  epidemic  diseases  which  in  succession  sorely  afflicted 
the  colonies,  namely  smallpox  by  Labdiel  Boylston,  diphtheria  by 
Samuel  Bard,  and  yellow  fever  by  Matthew  Carey,  William  Currie, 
and  Benjamin  Rush.  Samuel  Bard's  "Enquiry  into  the  Nature, 
Cause  and  Cure  of  the  Angina  Suffocativa  or  Sore  Throat  Dis- 
temper," William  Currie*s  "Historical  Account  of  the  Climates  and 
Diseases  of  the  United  States,"  and  Noah  Webster's  "  Brief  History 
of  Epidemic  and  Pestilential  Diseases,"  are  the  works  of  greatest 
permanent  value  to  medicine  published  in  this  country  before  the 
close  of  the  eighteenth  century,  although  we  cherish  John  Morgan's 
"Discourse  upon  the  Institution  of  Medical  Schools  in  America" 
as  a  precious  document  of  our  medical  literature. 

While  Philadelphia  was  the  medical  center  of  America  in  the 
eighteenth  century  and  later,  and  the  names  of  its  medical  leaders — 
Colden,  Cadwalader,  Bond,  Morgan,  Shippen,  Jones,  Redmond, 
Rush,  Wistar,  Kuhn — sufficiently  indicate  their  origin,  there  was 
no  more  cultivated  and  attractive  group  of  medical  men  in  the  third 
quarter  of  the  eighteenth  century  in  America  than  that  in  Charles- 
ton, S.  C,  which  has  been  so  well  pictured  by  Mumford.  Of  these 
Bull  was  a  pupil  of  Boerhaave,  and  Chalmers,  Moultrie,  Lining,  and 
Garden  were  trained  in  Edinburgh.  These  men  were  abreast  of  the 
knowledge  of  the  day;  some  were  naturalists  as  well  as  physicians, 
their  names  being  perpetuated  in  those  of  plants,  fellows  of  the 
Royal  Society,  and  correspondents  of  Linnaeus,  Fothergill,  and 
other  European  savants. 

After  the  Revolution  American  medicine  assumed  a  character 
of  greater  independence  and  reliance.  Elihu  Hubbard  Smith,  the 


li 


ENGLISH   AND   AMERICAN   MEDICINE  813 

father  of  American  medical  journalism,  established  in  1797  The 
Medical  Repository y  which  survived  until  four  years  after  the  founda- 
tion in  1820  of  the  journal  now  known  as  the  American  Journal  of 
the  Medical  Sciences. 

The  most  important  channel  of  foreign  influence  is  that  of  edu- 
cation, and  it  is  fortunate  that  so  vigorous  and  healthy  an  influence 
as  that  of  the  University  of  Edinburgh  inspired  the  ideas  of  Morgan, 
Shippen,  Bard,  Hosack,  and  other  founders  of  medical  education 
in  this  country,  who  had  been  taught  by  CuIIen,  the  Munros,  Black, 
the  Hamiltons,  Gregory,  the  Bells,  and  other  leaders  of  the  Edin- 
burgh School.  These  were  the  influences  which  presided  over  the 
foundation  of  the  Medical  School  of  the  College  of  Philadelphia — 
later  the  University  of  Pennsylvania — in  1765,  and  that  of  Kings 
College — later  Columbia  University — in  1768.  We  should  always 
recall  with  gratitude  the  deep  interest  and  support  and  advice  of 
CuIIen  and  of  John  Fothergill  and  later  Lettsom,  the  delightful 
Quaker  physicians  in  London,  who  were  the  friends,  counselors,  and 
correspondents  of  so  many  American  medical  students  and  phy- 
sicians in  the  latter  part  of  the  eighteenth  century. 

The  rise  in  the  nineteenth  century  of  the  many  detached  pro- 
prietary medical  schools  scattered  over  the  land,  sometimes  in  small 
country  towns,  is  a  phase  in  our  medical  history,  peculiar  to  the 
United  States,  which  we  cannot  contemplate  with  satisfaction. 
Acquaintance  with  the  separate  medical  schools  in  London  in  the 
later  eighteenth  and  early  nineteenth  centuries,  such  as  the  famous 
Great  Windmill  Street  School,  founded  by  William  Hunter,  Shel- 
don's Great  Queen  Street  School,  Marshal's  School  at  Thavies* 
Inn,  Brooks's  School,  the  Webb  Street  School,  the  Little  Dean 
Street  School,  and  others  frequented  by  American  students,  may 
have  had  some  influence,  but  neither  these  nor  the  hospital  schools 
in  London  were  empowered  to  grant  the  doctor's  degree  nor  the 
license  to  practice,  and  we  must  recognize  the  movement  for  separate 
schools  as  in  the  beginning  a  response  to  the  urgent  needs  of  the 
country  for  a  rapid  supply  of  physicians. 

Objectionable  as  the  system  was  in  many  respects,  and  inexcus- 
ably long  as  it  lasted,  the  results  were  better  than  might  have  been 
anticipated,  as  defects  were  in  a  measure  counterbalanced  by  the 
devotion  of  excellent  teachers  and  by  the  native  intelligence  and 


8i4  ENGLISH   AND   AMERICAN   MEDICINE 

industry  of  the  pupils.  A  unique  product  of  these  local  conditions 
was  the  peripatetic  professor,  strikingly  exemplified  in  the  person 
of  John  Delamater. 

The  influence  of  English  as  distinguished  from  Scottish  Medicine 
upon  America  was  most  marked  in  the  latter  part  of  the  eighteenth 
and  the  first  three  decades  of  the  nineteenth  centuries.  This  came 
largely  from  the  great  London  surgeons,  Percival  Pott  and  John 
Hunter  and  their  successors,  especially  Abernethy  and  Sir  Astley 
Cooper. 

John  Jones,  who  begins  the  line  of  American  surgeons  with  his 
book  for  army  surgeons  entitled  "Plain  Remarks  upon  Wounds 
and  Fractures,"  published  just  before  the  Revolutionary  War,  had 
been  a  pupil  of  Percival  Pott.  John  Morgan,  Richard  Bayley,  and 
William  Shippen,  Jr.,  studied  under  William  or  John  Hunter.  The 
list  of  American  pupils  of  Sir  Astley  Cooper  is  a  long  one,  and  in- 
cludes the  names  of  John  Collins  Warren,  James  Jackson,  Valentine 
Seaman,  Valentine  Mott,  Dorsey,  William  Gibson,  Alexander  H. 
Stevens,  John  Kearny  Rodgers,  Edward  Delafield,  B.  W.  Dudley 
(also  a  pupil  of  Larrey),  John  Wagner,  and  others.  Physick  was 
almost  as  much  a  mouthpiece  of  the  doctrines  of  John  Hunter  in 
America  as  Abernethy  was  in  London. 

As  the  Munros  prevented  the  establishment  of  a  chair  of  surgery 
in  the  University  of  Edinburgh  until  well  into  the  nineteenth  cen- 
tury, although  John  Bell  was  an  excellent  extramural  teacher, 
early  American  surgery  was  derived  mainly  from  the  London  group, 
and  to  this  we  may  attribute  the  interest  in  anatomy,  normal  and 
pathological,  which  has  characterized  American  surgery.  We  owe 
to  a  surgeon,  the  elder  Gross,  the  first  American  treatise  on  morbid 
anatomy. 

Matthew  Baillie's  classical  work  on  morbid  anatomy  led  in 
England,  as  Bichat's  did  in  France,  in  the  early  nineteenth  century 
to  the  first  fruitful  combination  of  clinical  and  pathological  studies, 
culminating  in  Richard  Bright's  "Reports  of  Medical  Cases" 
published  in  1827.  From  both  sources  sprang  the  new  era  which 
now  arose  in  America,  but  it  was  from  pupils  of  Louis,  namely 
Gerhard,  aided  by  Stille,  the  younger  Jackson,  and  Shattuck,  that 
there  came  America's  great  contribution,  resting  upon  combined 
clinical  and  pathological  investigations,  of  the  sharp  and  decisive 


ENGLISH   AND   AMERICAN   MEDICINE  815 

distinction  between  typhus  and  typhoid  fevers,  following  which 
Elisha  Bartlett  published  the  first  modern,  systematic  treatise  on 
fevers  based  upon  the  new  doctrines. 

Results  of  the  remarkable  development  of  ophthalmology  in 
England  in  the  early  nineteenth  century  by  the  work  of  Saunders, 
Adams,  Travers,  Lawrence,  and  Mackenzie  were  brought  to  the 
United  States  by  Edward  Delafield,  who  with  Rodgers  founded  the 
New  York  Eye  and  Ear  Infirmary  in  1820.  As  early  as  1823  George 
Frick  published  in  Baltimore  the  first  original  American  treatise 
on  the  diseases  of  the  eye. 

The  great  reform  in  clinical  teaching  by  Graves  and  Stokes  in 
Dublin,  transmitted  to  London  by  Robert  Bentley  Todd,  had  a 
marked  influence  in  America,  where  Graves*  "Clinical  Lectures," 
the  most  famous  ever  published  in  English,  had  an  enormous  vogue 
at  about  the  same  period,  when  Sir  Thomas  Watson's  "Practice" 
and  C.  J.  B.  Williams*  "Principles  of  Medicine**  were  the  admirable 
and  favorite  text  books. 

While  America  has  not  produced  a  Harvey,  a  Sydenham  or  a 
John  Hunter,  one  can  recognize  readily  the  lineage  and  the  features 
of  familiar  types  of  English  physicians  and  surgeons  in  conspicuous 
members  of  the  medical  profession  of  this  country. 

Benjamin  Rush,  the  greatest  historical  figure  in  American  medi- 
cine, has  been  called  with  singular  inappropriateness  "the  American 
Sydenham.'*  He  belongs  rather  to  a  type  not  congenial  to  English 
soil,  the  eighteenth  century  systematists,  of  whom  CuIIen  and 
Brown,  whose  disciple  he  was,  are  the  chief,  as  well  as  the  last 
British  representatives.  There  was  much  more  of  that  objective 
naturalistic  study  of  disease,  unhampered  by  tradition  and  dogma, 
which  characterized  Sydenham,  to  be  found  in  the  works  of  Nathan 
Smith,  Daniel  Drake,  and  Jacob  Bigelow.  Physick,  Mott,  the  War- 
rens, bear  favorable  comparison  with  their  contemporaries  in  English 
surgery.  Of  the  humanistic  type  and  of  the  lineage  of  Mead,  Garth, 
and  Arbuthnot  were  Hosack  and  his  pupil  Francis,  interested  in 
letters  and  natural  history,  prominent  in  social  life,  withal  excellent 
teachers  and  physicians,  worthy  to  have  inherited  the  gold-headed 
cane  had  Matthew  Baillie  sent  it  across  the  Atlantic  to  New  York. 
Bartlett,  the  elder  Jackson,  Alonzo  Clark,  and  the  elder  Flint 
belonged  to  the  EngHsh  type  of  sane,  judicious,  objective  clinicians^ 


8i6         ENGLISH   AND   AMERICAN   MEDICINE 

More  picturesque  and  more  distinctive  of  conditions  then  existing 
in  America  was  the  group  of  physicians  and  surgeons,  of  whom 
McDowell,  Dudley,  and  Drake  were  the  leaders,  who  lived  in  the 
early  part  of  the  nineteenth  century  on  the  frontier  on  or  near  the 
banks  of  the  Ohio.  While  abreast  in  knowledge  and  skill  with  the 
best  in  contemporary  medicine,  they  had  all  the  indomitable  pluck, 
the  resourcefulness,  and  the  native  vigor  of  mind  and  body  which 
characterized  the  pioneers  who  won  the  West. 

There  has  been  no  analogy  in  America  to  the  London  hospital 
medical  schools.  These  have  their  shortcomings  as  well  as  good 
features,  but  efforts  to  unify  and  to  prove  them  do  not  encounter 
one  of  the  main  difficulties  in  improving  medical  education  in 
America,  where  hospitals  and  medical  schools  originated  and  were 
developed  apart  from  each  other  and  the  need  of  their  affiliation  or 
union  meets  serious  obstacles.  The  admirable  system  of  dressers 
and  cfinical  clerks  found  in  British  hospitals  was  introduced  first  in 
America  by  Osier  at  the  Johns  Hopkins  Hospital. 

Nothing  has  been  more  remarkable  during  the  last  generation 
in  American  medicine  than  the  estabfishment  of  independent 
institutions  for  medical  research  and  the  rapid  improvement  in 
medical  education,  so  that  our  country  in  opportunities  for  the 
training  of  students  and  the  promotion  of  knowledge  compares 
favorably  with  those  of  Europe. 

In  these  last  remarks  I  have  passed  beyond  the  historical  period 
set  for  this  paper.  It  would  transgress  both  this  and  the  limits  of 
space  allowed  were  I  to  attempt  to  speak  of  the  important  influence 
up>on  American  physiology  of  one  of  the  glories  of  modern  English 
medicine,  its  school  of  physiology,  or  of  the  great  developments  in  the 
organization  and  administration  of  public  health,  in  which  England 
leads  the  world,  although  in  this  field  America  too  has  made  valuable 
original  contributions. 

One  of  the  results  of  the  Great  War  has  been  to  direct  attention 
forcibly  to  the  state  of  science,  medicine,  and  public  hygiene  in  the 
leading  countries  of  the  civilized  world  with  the  view  of  profiting 
by  the  lessons  of  the  war  and  of  readjustment  to  profoundly  changed 
internal  and  international  conditions.  The  minds  of  both  the  pro- 
fession and  the  public  have  been  awakened  to  the  need  of  improve- 
ment in  education  and  practice  in  science,  medicine,  and  public 


I 


ENGLISH   AND   AMERICAN   MEDICINE         817 

health,  of  ampler  provision  for  advancing  and  applying  useful 
knowledge,  and  of  establishing  between  countries  recently  asso- 
ciated in  the  war  closer  scientific  relations  and  better  reciprocal 
opportunities  for  graduate  study.  Considerations  such  as  these  make 
it  well  to  recall  the  intimate  association  of  British  medicine  and 
American  medicine  in  the  past  and  to  look  forward  to  a  future  of 
mutual  helpfulness  in  which  America  may  be  able  to  repay  a  part 
of  her  debt  to  British  medicine. 


THE  EYES  OF  THE  BURROWING  OWL 

WITH   SPECIAL   REFERENCE   TO   THE    FUNDUS   OCULI 

By  Casey  A.  Wood,  M.D.,  Chicago,  III. 

OF  all  the  Strigf formes  there  is  none  so  interesting  from  the 
standpoint  of  the  visual  apparatus  as  that  widely  distrib- 
uted New  World  group — the  Burrowing  Owls.  These  birds 
are  found  (as  the  typical  species,  Speotyto  cunicularia)  throughout 
the  pampas  regions  of  Central  South  America  and  occasionally  far- 
ther south;  and  are  well  known,  as  a  subspecies,  in  Florida  {Speotyto 
c.  floridana)y  the  West  India  Islands,  and  on  the  plains  and  in  the 
valleys  of  North  America  (Speotyto  c.  bypogaea)  as  far  north  as 
British  Columbia. 

Of  the  numerous  subspecies  may  be  mentioned  also  the  small, 
pale-brown,  insectivorous,  Short-Winged  Burrowing  Owl  (Speotyto 
c.  hracbyptera)  inhabiting  the  island  of  Santa  Margarita,  Venezuela; 
and  the  Haitian  form — Speotyto  c.  dominicensis.  The  Florida  Owl 
is  also  seen  in  the  Bahamas.  Although  smaller  than  the  typical 
species,  it  has  larger  feet  and  bill;  the  plumage  is,  on  the  whole, 
darker,  with  clear  white  spots. 

All  Burrowing  Owls  are  comparatively  small  (less  than  1 1  inches 
in  length),  but  this  peculiarity  is  not  so  noticeable  on  account  of 
their  unusually  long,  bare  legs.  Their  habits  are  said  to  be  mainly 
diurnal,  but  observations  of  the  North  American  species  by  the 
writer  incHne  him  to  the  belief  that  they  are  essentially  nocturnal 
animals,  like  most  owls.  Burrowing  habits  seem  to  be  common  to 
all  the  species. 

Burrowing  owls  have  a  dull-brownish,  spotted,  and  barred 
plumage;  the  middle  of  the  chest  is  white  and  is  partly  encircled  by 
a  plainly  marked  buff-brown  collar.  The  head  is  rather  flat  and  small, 
the  facial  disks  are  not  well  defined,  the  bill  is  short,  and  the  wings 
are  relatively  undeveloped,  so  the  bird  is  able  to  fly  only  short 
distances. 

8i8 


THE  EYES  OF  THE  BURROWING  OWL  819 

The  food  of  these  owls  consists  almost  entirely  of  mice,  gophers, 
and  similar  mammals,  as  well  as  of  small  reptiles  and  insects.  Of 
these  a  family  of  owls,  commonly  ten  in  number,  will  consume 
enormous  quantities;  each  member  disposing  of  his  own  weight 
of  pabulum  in  twenty-four  hours! 

According  to  Knowlton  and  Ridgway  (i)  the  Burrowing  Owl  is 
more  or  less  migratory,  and  after  a  return  to  its  usual  habitat  mates 
(probably  for  life)  and  then  arranges  its  underground  nest.  The 
contour  of  these  nesting  burrows  varies;  they  are  usually  about  15 
inches  wide  and  from  5  to  10  feet  in  length.  They  enter  the  ground 
in  a  diagonal  direction  for  a  few  feet  and  then  turn  at  an  angle  either 
to  the  right  or  to  the  left.  The  nesting  chamber  (12  to  18  inches  in 
width),  placed  at  the  highest  part  of  the  burrow,  is  mostly  lined 
with  dry  dung,  but  sometimes  with  hair,  feathers,  or  dried  grass. 
The  eggs  are  six  to  twelve  (generally  eight)  in  number;  their 
color,  when  unsoiled,  is  glossy  white. 

It  must  be  remembered  that  while  the  great  majority  of  these 
owls  dig  their  own  burrows,  many  of  them,  especially  the  northern 
varieties,  make  use  of  the  abandoned  holes  of  certain  mammals, 
notably  of  the  prairie  dog,  fox,  badger,  skunk,  and  ground  squirrel. 
Doubtless  in  the  latter  instances  the  Burrowing  Owl  may  enlarge 
or  otherwise  alter  the  size,  length,  and  other  dimensions  of  the  newly 
acquired  hole. 

The  Burrowing  Owl  is  not  over-clean  in  his  habits;  the  nesting 
chamber  and  the  remainder  of  the  burrow  are  often  filthy  and  foul 
smelling. 

The  writer  has  studied  the  habits  of  the  North  American  and 
Florida  subspecies,  with  special  attention  to  the  eyes  and  eyesight 
of  the  bird.  From  these  observations  he  concludes  that  this  owl, 
like  all  the  others,  is  a  true  night  bird,  adapting  itself  with  but  slight 
success  to  daylight  conditions.  In  spite  of  the  fact  that  Bendire  and 
Hudson  refer  to  the  animal  as  a  diurnal  owl,  their  accounts  of  its 
habits  really  bear  out  the  writer's  contention  of  a  nocturnal  animal 
with  fairly  good  day  vision,  yet  distinctly  embarrassed,  uncertain, 
and  confused  when  the  eyes  are  exposed  to  bright  sunlight.  Stress 
is  laid  by  a  number  of  observers  upon  the  fact  that  this  owl  is  seen 
at  all  times  of  the  day  standing  guard,  often  on  a  little  mound  of 
earth  in  front  of  his  burrow  entrance,  forgetting  that,  as  a  much 


020  THE  EYES  OF  THE  BURROWING  OWL 

more  interested  householder,  he  also  watches  from  the  same  post 
all  hours  of  the  night! 

Bendire  gives  the  best  account  of  their  habits  as  observed  by  a 
daylight  student  of  their  habits: 

"When  not  unduly  molested,  they  are  not  all  shy,  and  usually  allow 
one  to  approach  them  near  enough  to  note  their  curious  antics.  Their 
long,  slender  legs  give  them  a  rather  comical  look — a  sort  of  top-heavy 
appearance.  Should  you  circle  around  them  they  will  keep  you  constantly 
in  view,  and  if  this  is  kept  up  it  sometimes  seems  as  if  they  were  in  danger 
of  twisting  their  heads  off  in  attempting  to  keep  you  in  sight.  Tbey  bunt 
their  prey  mostly  in  the  early  evening  and  throughout  the  night,  more  rarely 
in  the  daytime.  As  soon  as  the  sun  goes  down  they  become  exceedingly 
active  and  especially  so  during  the  breeding  season. " 

As  one  result  of  a  rather  extensive  study  of  the  visual  apparatus 
of  this  interesting  owl,  the  writer  has  never  seen  anything  to  convince 
him  that  the  bird  ever  performs  an  act  requiring  distinct  diurnal 
vision.  Certainly  the  northern  bird  is  decidedly  nocturnal,  occasion- 
ally using  his  eyes,  but  at  a  disadvantage,  during  daylight  hours. 

This  conclusion  is  confirmed  in  a  noteworthy  fashion  by  a  com- 
parison of  the  fundus  oculi  of  this  owl  with  the  same  picture  in 
owls  entirely  nocturnal  in  their  habits,  and  indeed  with  certain 
other  evidence  (especially  that  they  all  show  orange  or  reddish 
fundi)  constantly  found  in  night  animals. 

These  facts  have  been  fully  stated  by  G.  Lindsay  Johnson  (2) 
as  regards  the  mammalia;  and  by  the  writer  (3)  for  the  avian  eye. 

As  in  all  owls,  the  eyeballs  are  set  well  in  front  and  surrounded 
by  more  or  less  plainly  marked,  uniform  and  complete  facial  disks 
(that  probably  act  as  reflectors  into  the  eye  of  the  diffused  and 
faint  rays  of  evening  light). 

Strigiform  eyes  more  closely  than  those  of  any  other  order  re- 
semble human  eyes;  and  they  preserve,  as  in  man,  about  the  same 
relation  to  other  facial  organs  and  are  so  placed  as  to  obtain  binocular 
vision  in  front.  Structurally,  of  course,  birds'  eyes  are  quite  different, 
especially  in  the  morphology  of  the  eyeball,  in  the  possession  by  the 
owl  of  a  pecten  instead  of  retinal  vessels,  in  the  covered  optic  nerve 
and  in  many  other  particulars  which  it  is  not  proper  to  specify  here. 

Slonaker  (4)  and  the  writer  (5)  have  pointed  out  that  all  the 
owls  are  exceptions  to  the  rule  that  the  retinal  area  of  distinct  vision 


The  Fundus  Oculi  of  the  Burrowing  Ovri—Speotyto  cunicularia  hypogoea. 


THE  EYES  OF  THE  BURROWING  OWL 


821 


is  in  birds  with  a  single  fovea  placed  above  and  towards  the  ncLsal 
aspect  of  the  optic  nerve  entrance.  The  owls  possess  a  single,  deep 
fovea  encircled  by  a  round,  sharply  defined  area  located  above 
and  on  the  temporal  side  of  the  optic  disk.  This  arrangement  closely 
approaches  the  binocular  maculae  of  man. 

The  writer  gives  to  the  owls  a  class  by  itself  in  describing  these 
areae  and  affirms  that  the  temporal  monomacular  fundus  is  found 
almost  exclusively  in  the  owls. 

In  conjunction  with  Arthur  W.  Head,  F.  Z.  S.,  the  South  Ameri- 
can Burrowing  Owls  in  the  London  Zoological  Gardens  were  closely 
studied  and  examined  with  the  ophthalmoscope.  In  addition,  the 
interior  of  the  eyeball     . 
both  of  that  type  and 
of  several  North  Amer-  . 
ican  individuals  were 
examined  by  the  writer 
in  prepared  specimens. 

The  ophthalmo- 
scope in  particular 
shows  the  fundus  oculi 
of  Speotyto  cunicularia 
to  be  that  of  a  typical 
nocturnal  animal.  The 
picture  of  this  bird's 
background  is  well  shown  in  the  accompanying  colored  plate, 
painted  by  Head  and  faithfully  reproduced  here.  The  ocular 
fundus  of  this  species  is  irregularly  round,  as  in  all  the  owls,  and 
in  prepared  specimens  these  details  show  distinctly. 

The  single,  temporal,  oval  macular  region  hes  above  and  about 
a  disk  length  and  a  half  from  the  upper  end  of  the  papilla.  In  the 
center  of  the  macula  is  the  fovea — a  dark  pigmented  spot  with  fine 
granules  arranged  cap-Hke  above  it.  Outside  this,  again,  is  the  ovoid 
circumference  of  this  region,  incompletely  edged  with  fine  dots. 
These  are  more  numerously  distributed  below  the  macula  than 
above  it.  Connected  with  the  macular  region  is  a  light-colored  and 
rather  broad  band  that  extends  horizontally  to  the  center  of  the 
visible  background.  It  is  unevenly  divided  into  two  strips  by  a 
parallel  arrangement  of  minute  pigment  dots. 


Lateral  View  of  the  Pecten  of  the  Burrowing  Owl — 
Speotyto  cunicularia  bypogxa.     x  9. 


822  THE  EYES  OF  THE  BURROWING  OWL 

Seen  from  above,  the  relatively  small  pecten  closely  resembles  a 
disarticulated,  acuminate  leaf,  the  stem  representing  the  spinous 
projection  immediately  above  the  lowest  terminal  convolution.  The 
light  double  folds  of  the  marsupium  slope  backwards  and  cover  most 
of  the  optic  entrance;  they  meet  above  in  a  uniform,  very  narrow, 
slightly  undulating  crest  whose  posterior  end  projects  half  the  height 
of  the  underlying  coil  well  into  the  vitreous  cavity.  An  extension 
upwards  of  the  long  axis  of  the  disk  cuts  the  retinal  band  at  the 
junction  of  the  inner  and  second  fourth,  making  an  infulapapillary 
angle  of,  perhaps,  40°. 

This  interesting  owl  is  especially  subject,  like  other  Strigiformes, 
to  pathological  variations  in  the  fundus  picture  after  confinement 
and  domestication.  Both  Head  and  the  writer  examined  a  number 
of  individuals  that  undoubtedly  exhibited  choroidal  disease  and 
other  pathological  changes.  Rejecting  these,  the  general  color  of 
the  fundus  of  this  species  is  found  to  be  dull-orange,  mottled  and 
blotched  in  its  upper  half  with  deep  orange-red.  Choroidal  vessels 
are  plainly  visible,  covering  all  the  lower  part  of  the  eyeground,  just 
as  in  the  Tawny  Owl.  The  well-defined  macular  area  is  seen  within 
the  outer  half  of  the  fundus,  a  little  above  the  upper  extremity  of 
the  optic  disk.  It  is  distinguished  from  the  surrounding  choroid  by 
a  collection  of  minute  pigment  granules  or  dots  with  a  bright,  white 
spot  in  their  center. 

The  optic  disk  is  white  and  of  oblong  shape,  slightly  rounded  at 
the  ends.  From  its  edges  run  a  few  short  nerve  fibers  that  form  a 
complete  fringe  about  the  visible  papilla. 

The  pecten  is  decidedly  larger  in  proportion  to  bodily  measure- 
ments than  one  finds  it  in  most  of  the  larger  owls,  especially  larger 
than  in  the  Tawny  Owl.  It  extends  well  forward  into  the  vitreous, 
and  its  lower  half  appears  very  massive  and  of  a  dark  brown  color. 
The  pectinate  convolutions  are  plainly  seen  and  the  anterior  or 
upper  half  is  more  delicate  in  structure,  being  perforated  where  it 
joins  the  disk.  Here  it  forms  a  dark  network  on  the  surface  of  the 
nervehead,  where,  also,  a  few  red  granules  mingle  with  the  chocolate- 
brown  texture  of  the  pecten. 


THE  EYES  OF  THE  BURROWING  OWL  823 

BIBLIOGRAPHY 

1.  "Birds  of  the  World,"  p.  537. 

2.  Phil.  Tr.,  Lond.,  1901. 

3.  "Fundus  Oculi  of  Birds,"  Chicago,  19 17. 

4.  Jr.  Morpb.,  1897,  XIII,  445. 

5.  Am.  Encyc.  Opbtb.,  1914,  IV,  2519. 


THE  REGULATION  OF  THE  RED  BLOOD-CELL 

SUPPLY 

By  C.  H.  Bunting,  M.D.,  Madison,  Wis. 

(From  the  Pathological  Laboratory  of  the  University  of  Wisconsin) 

A  MONG  the  many  problems  oflFered  by  the  hematopoietic 
/-\  system,  that  of  the  regulation  of  the  red  blood-cell  supply 
JL  jLto  the  circulation  is  not  the  least  interesting.  For  weeks, 
months,  and  even  years  of  health,  an  individual  man  or  animal  has 
a  peripheral  red-cell  count  which  is  for  all  practical  purposes  a 
constant.  This  constant  is  maintained  in  spite  of  a  wear  and  tear 
which  results  in  the  daily  destruction  of  a  not  inconsiderable  pro- 
portion of  the  total  number  of  circulating  red  cells.  Its  maintenance 
requires  the  production  and  the  supply  to  the  circulation  of  an  equal 
number  of  new  cells  daily.  These  new  cells  are  produced  in  the  ery- 
throgenic  centers  within  the  bone-marrow  and  outside  of  the  cir- 
culation. Devoid  of  active  ameboid  motion,  they  must  pass 
through  the  endothelial  lining  of  the  vessels  to  enter  the  blood 
stream  by  means  of  some  force  developed  outside  of  themselves — 
some  VIS  a  t^go — and  in  the  nature  of  that  force  lies  the  question  of 
the  control  of  the  red  blood-cell  supply.  What  is  the  impelling  force 
which  pushes  enough  cells  into  the  circulation  per  unit  of  time  to 
maintain  the  blood  count  at  its  level?  Obviously  one  must  seek  for 
a  mechanical  cause. 

One  may  gain  a  hint  as  to  the  direction  in  which  to  push  his 
inquiry  by  a  consideration  of  the  rate  of  supply  of  red  blood  cells 
to  the  circulation.  While  the  absolute  length  of  life  of  a  circulating 
red  cell  is  not  known,  Zoja  (i)  and  others  have  estimated  that  one- 
tenth  of  all  the  hemoglobin  in  the  body  is  destroyed  each  twenty- 
four  hours.  This  conclusion  was  reached  by  the  determination  of  the 
amount  of  hemoglobin  which  was  represented  in  the  daily  excretion 
of  bile  pigment;  and  it  assumes  that  all  the  bile  pigment  is  derived 
from  hemoglobin,  an  assumption  upon  which  doubt  has  been  cast 
by  Whipple  and  Hooper.  (2)  However,  for  the  sake  of  argument,  one 
may  disregard  their  criticism.  If  one-tenth  of  all  the  hemoglobin  is 
broken  down  each  day,  it  can  happen  only  with  the  destruction  of 

824 


REGULATION  OF  RED  BLOOD-CELL  SUPPLY      825 

one-tenth  of  all  the  red  blood  cells.  In  other  words,  the  life  of  a  red 
cell  is  approximately  ten  days.  If  an  adult  man  possesses  approx- 
imately 5  liters  of  blood  and  5,000,000  red  cells  per  cu.  mm.,  he 
must  have  in  his  circulation  in  the  neighborhood  of  25,000,000,000 
red  cells,  and  with  the  destruction  of  one-tenth  of  these  an  equal 
number,  2,500,000,000,  must  be  produced  each  day  in  order  to 
maintain  his  constant  count.  A  simple  mathematical  operation 
demonstrates  that  if  this  rate  of  production  be  true  the  marrow  must 
furnish  to  the  circulation  approximately  28,935,000  red  cells  per 
second  of  time.  This  rate  of  activity  on  the  part  of  the  bone  marrow 
is  almost  unbelievable,  yet  were  the  length  of  life  of  the  red  cell 
fifty  days,  one  would  get  the  scarcely  less  preposterous  rate  of 
5,787,000  cells  per  second  as  the  number  that  must  be  pwroduced  to 
maintain  the  constant. 

That  these  figures  lie  close  to  the  realm  of  truth  is  indicated  by 
figures  obtained  in  experiments  upon  animals.  In  a  series  of  experi- 
ments performed  a  number  of  years  ago  (3)  in  which  rabbits  were  bled 
a  small  amount  daily,  I  found  that  if  the  bleeding  was  omitted  for  a 
day  the  blood  count  would  increase  500,000  cells  per  cu.  mm.  A 
rabbit  of  two  kilograms  in  weight  has  approximately  100  cm.  of 
blood,  and  so  apparently  is  able  (with  hyperplastic  marrow,  it  is 
true)  to  produce  50,000,000,000  red  cells  in  twenty-four  hours  in 
addition  to  those  lost  in  the  daily  wear  and  tear. 

These  figures  suggest  a  continuity  of  action  on  the  part  of  the 
bone  marrow,  and  this  is  further  indicated  by  the  rapid  response  by 
the  marrow  with  nucleated  red  cells  after  marrow  injury.  In  a  recent 
experiment  a  rabbit  was  given  an  intravenous  dose  of  4  mg.  of 
saponin,  after  blood  smears  had  been  carefully  searched  for  nu- 
cleated red  cells  with  negative  result.  The  experimental  data  are 
as  follows: 

Rabbit,  albino,  wt.  1545. 

11:10  A.M.  R.b.c.  6,476,000,  W.b.c.  8000.  No  nucleated  reds  found 
in  smear.  4  mg.  saponin  given  in  ear  vein. 

1 1 140  A.M.  scattered  normoblasts  found. 

1 1 :58  A.M.  W.b.c.  8000,  64^  nucleated  reds  per  cu.  mm. 

12:18  P.M.  W.b.c.  8000,  256  nucleated  reds  per  cu.  mm. 
2  P.M.  W.b.c.  7500,  1045  nucleated  reds  per  cu.  mm. 

^  Number  estimated  from  the  number  seen  in  counting  500  white  cells  in  smear 
preparation. 


826      REGULATION  OF  RED  BLOOD-CELL  SUPPLY 

Here  we  have  indication  of  a  very  prompt  reaction  to  the  injury, 
with  the  appearance  of  a  few  normoblasts  within  one-half  hour,  and 
a  large  number  (1045  per  cu.  mm.)  within  three  hours. 

In  what  way,  it  may  be  asked,  do  these  figures  aid  in  the  solution 
of  the  problem  of  the  red  blood-cell  supply?  First,  they  show  defi- 
nitely that  to  deliver  the  number  of  cells,  indicated  as  that  demanded 
per  unit  of  time,  the  marrow  activity  cannot  be  other  than  constant. 
There  must  be  a  constant  outpouring  of  cells  and  not  the  occasional 
pushing  of  a  cell  into  the  blood  stream. 

In  the  second  place,  while  they  do  not  reveal  absolutely  the 
eflfective  delivery  force,  they  indicate,  when  taken  in  connection 
with  marrow  structure,  what  it  must  be.  It  is  my  intention  to  enter 
into  a  description  of  marrow  structure  at  this  point  only  so  far  as 
may  be  of  value  in  elucidating  the  problem  at  hand.  The  marrow  is 
an  extremely  labile,  plastic  organ  enclosed  in  a  cavity  with  rigid 
bony  walls  which  give  it  fixed  dimensions.  This  would  seem  to  be  an 
adaptation  not  without  purpose.  The  organ  itself  consists  of  a  blood- 
vascular  system,  fat  cells,  and  the  blood-forming  elements  supported 
by  a  reticulum,  and  is  without  white  fibrous  elements  except  in  the 
adventitia  of  the  arterioles.  The  circulation,  as  revealed  by  natural 
injections  of  the  rabbit's  marrow,  is  unlike  that  of  any  other  organ, 
but  resembles  superficially  that  of  the  spleen  pulp.  There  is  no 
capillary  net-work.  Slender  arterioles  or  arterial  capillaries  run  from 
their  origin  near  the  center  of  the  marrow,  without  capillary  side 
branches  or  anastomoses,  to  the  extreme  periphery,  where  they 
open  into  wide  thin-walled  venous  sinuses.  These  in  turn  run  toward 
the  marrow  center,  uniting  with  their  adjacent  fellows  in  pyramidal 
clusters,  suggestive  of  the  vascular  tufts  of  granulation  tissue,  and 
eventually  forming  large  collecting  veins  which  empty  into  the 
central  vein  at  regular  intervals  of  about  i  mm.,  as  shown  by  longi- 
tudinal marrow  sections.  The  arterial  vessels  are  quite  thick-walled. 
The  sinuses,  on  the  other  hand,  have  endothelial  walls  of  extreme 
tenuity,  and  it  must  be  these  vessels  that  the  blood  cells  enter. 
Between  these  venous  sinuses  are  the  fat-cells  and  the  hemopoietic 
groups. 

It  is  to  changes  in  pressure  relations  in  one  of  these  three  elements 
that  one  must  look  for  the  force  which  pushes  the  red  cells  into  the 
venous  sinuses.  It  would  seem  that  there  must  be  created  an  extra- 


REGULATION  OF  RED  BLOOD-CELL  SUPPLY      827 

venous  pressure  which  must  be  of  quite  constant  nature.  While  the 
state  of  the  fat-content  of  the  marrow-fat  cells  changes,  we  cannot 
conceive  of  a  constant  activity  in  this  element  which  would  produce 
the  result  seen.  In  considering  the  possible  role  of  the  vascular 
system  in  the  production  of  the  phenomenon  under  consideration, 
one  must  recognize  that  changes  in  the  caliber  of  the  vessels  do  occur. 
These  are  in  the  main,  however,  changes  that  take  place  over 
a  relatively  long  space  of  time  and  are  concerned  apparently  with 
various  degrees  of  hyperplasia  of  the  marrow  and  can  have  nothing 
to  do  with  the  constant  normal  emigration  of  cells.  The  only  vascular 
change  that  might  be  of  importance  is  the  regular  occurrence  of  the 
pulse  wave  in  the  arterioles.  They  are  so  situated  in  the  midst  of 
the  hematopoietic  tissue  between  the  venous  sinuses  that  their  dilata- 
tion under  pulse  pressure  might  give  rise  to  sufficient  increase  in 
intersinus  pressure  to  force  red  cells  into  the  sinuses.  Yet  the  repe- 
tition of  that  impulse  would  fall  short  of  producing  the  same  effect 
without  one  further  factor  which  seems  to  me  most  vital.  That 
factor  lies  in  the  hematopoietic  cells  themselves.  The  hematopoietic 
tissue  is  far  from  inert.  Signs  of  cell-division,  in  mitotic  figures,  are 
numerous.  The  cells  are  constantly  increasing  in  number.  The  birth 
of  each  cell  must  increase  the  inter-vascular  tension,  and  to  make 
room  for  it  another  cell  must  leave,  and  by  the  only  available  route, 
the  blood-stream.  The  erythrogenic  groups  of  cells  of  the  marrow, 
as  well  as  the  leucogenic,  are  so  arranged  that  the  mature  differen- 
tiated cells  fie  on  the  periphery  of  the  groups,  so  it  is  these  cells 
that  would  be  pushed  into  the  circulation. 

It  would  seem,  therefore,  if  our  reasoning  be  true,  that  it  is 
the  rate  of  division  of  the  erythroblastic  cells  which  regulates  the 
output  of  red  ceils  from  the  marrow.  Further,  I  think  one  must 
assume,  in  view  of  the  figures  given  as  to  the  marrow  output,  that 
this  rate  is  constant  and  is  in  all  probability  the  maximum  rate 
for  a  given  amount  of  bone  marrow.  In  other  words,  in  health 
there  is  a  fixed  tempo  to  erythrogenic  tissue  profiferation;  and  thus 
the  number  of  red  cells  furnished  the  blood  stream  in  a  given  time 
is  a  "function"  of  the  amount  of  red  marrow  that  a  person  has. 
The  vis  a  tergo  which  pushes  the  cells  into  the  blood  stream  is  the 
increased  extravascular  pressure  caused  by  division  of  the  mother 
ceils  of  the  group.  Each  individual,  therefore,  apparently  acquires 


828     REGULATION  OF  RED  BLOOD-CELL  SUPPLY 

an  amount  of  red  marrow  which  at  the  given  rate  of  proliferation 
will  supply  to  the  circulation  the  number  of  cells  necessary  for 
his  daily  wear  and  tear.  That  this  tempo  is  the  maximum  rate  of 
production  seems  indicated  not  only  by  the  almost  impossible 
number  of  cells  produced,  but  by  another  finding.  When  an  added 
number  of  cells  is  required  in  the  circulation,  the  marrow  response 
is  not  immediate.  The  new  cells  are  furnished  only  after  a  delay, 
and  only,  as  shown  by  study  of  the  tissues,  after  an  extension  of 
red  marrow  has  taken  place.  This  extension  is  apparently  the 
result  of  dififerentiation  of  myeloblasts  into  erythroblasts  with  the 
formation  of  new  erythrogenic  centers.  This  increase  in  marrow 
elements  occurs  at  the  expense  of  the  adipose  tissue  cells  which 
give  up  their  fat.  This  possibly  accounts  for  the  lipemia  noted  by 
Boggs  and  Morris,  (4)  in  experimental  anemia  in  the  rabbit.  This 
extension  of  marrow  is  noted  in  all  anemias,  experimental  and 
clinical,  except  where  reaction  of  the  marrow  fails  (aplastic  anemia). 

The  stimulus  to  the  extension  of  marrow  seems  to  have  been 
conclusively  demonstrated  by  Dr.  Loevenhart  (5)  and  his  associates 
to  be  a  deficiency  of  oxygen.  In  atmospheres  of  diminished  oxygen 
content  there  is  a  marrow  extension  which  results,  after  an  interval, 
in  an  increase  in  the  peripheral  red-cell  count.  This  interval,  when 
taken  with  the  sections  of  the  marrow  (which  I  have  been  privileged 
to  study),  would  indicate  that  the  increase  was  not  due  to  a  change 
in  rate  of  proliferation  of  pre-existing  red  marrow,  but  to  the  normal 
tempo  applied  to  an  increased  amount  of  marrow.  This  is  confirmed 
further  by  the  fact  that  the  count  returns  slowly  to  normal  after 
the  animal  is  returned  to  an  atmosphere  of  normal  oxygen  content. 

The  evidence  at  hand,  then,  would  seem  to  indicate  that, the 
constancy  of  the  peripheral  red-cell  count  is  maintained  by  a 
maximum  activity  of  a  fixed  (for  normal  conditions)  amount  of  red 
bone-marrow,  and  that  the  active  force  producing  emigration  is  the 
force  exerted  by  division  and  growth  of  red-cell  progenitors. 

BIBLIOGRAPHY 

1.  Zoja,  Folia  Haematol,  19 10,  X,  232. 

2.  Whipple  and  Hooper,  J.  Exper.  M.,  1913,  XVII,  593. 

3.  Bunting,  J.  Exper.  M.,  1906,  VIII,  625. 

4.  Boggs  and  Morris,  Tr.  Ass.  Am.  Physicians,  1909,  XXIV,  467. 

5.  Dallwig,  KoIIs,  Loevenhart,  Am.  J.  Physiol,  1915,  XXXIX. 


THE  ACTION  OF  ADRENALIN  ON  THE  LEUCO- 
CYTES AND  ERYTHROCYTES 

A   CONSIDERATION  OF  THE  MECHANISM   BY  WHICH  THE   ACTION 

IS  BROUGHT  ABOUT 

By  David  Murray  Cowie,  M.D.,  Ann  Arbor,  Mich. 

(From  the  Department  of  Pediatrics  and  Contagious  Diseases, 
University  of  Michigan  Hospital) 

THE  symptom  of  marked  asthenia  so  prominent  in  the  recent 
epidemic  of  influenza  and  influenza  pneumonia,  together  with 
some  autopsy  findings  recorded  in  another  place,  (i)  sug- 
gested to  me  the  advisability  of  carrying  out  adrenalin  treatment 
in  a  series  of  such  cases,  not  with  the  idea  of  supporting  the  circu- 
lation, but  of  supplying  a  substance  which  we  assumed  was  lost  to 
a  greater  or  less  degree  by  the  eff'ect  of  the  infecting  agent  or  its 
toxin  up>on  the  chromaffin  tissues. 

While  pursuing  this  investigation,  my  attention  was  called  to 
the  work  of  Hatigan  (2)  on  the  changes  in  the  white  blood  cells 
caused  by  the  subcutaneous  injection  of  adrenahn.  We  were,  at  the 
same  time,  investigating  the  treatment  of  influenza  pneumonia  by 
the  intravenous  injection  of  non-specific  protein  (3)  (typhoid  pro- 
tein), particularly  because  of  the  efl"ect  of  the  protein  on  the  produc- 
tion of  leucocytes.  Hatigan's  report  led  me  to  investigate  this  point 
with  regard  to  adrenahn,  and  to  trace,  if  possible,  the  relation  of  the 
leucocyte  changes  induced  by  adrenahn  to  those  induced  by  ty- 
phoid protein. 

Order  of  Investigation.  Control  counts  were  made,  usuafly,  just  before 
and,  in  some  instances,  several  times  before  the  injection  of  adrenalin. 
After  the  injection,  counts  were  made  every  half  hour  for  two  hours  and 
every  hour  thereafter  until  the  leucocytes  returned  to  the  numbers  noted 
in  the  control  or  until,  for  other  reasons,  the  experiment  had  to  be  termi- 
nated.^ In  Case  XVII  counts  were  made  every  quarter  of  an  hour  after  the 
injection,  for  two  hours,  and  every  half  hour  thereafter.  In  those  cases 
in  which  food  was  taken  during  the  experiment,  it  is  so  noted  in  the 
records.    Differential   counts  were  made  with  1/12  oil-immersion  lens. 

*  Acknowledgment  is  due  to  my  interne,  Dr.  Campbell  Harvey,  for  his  painstaking 
assistance  in  making  total  leucocyte  counts.  Each  count  was  verified  by  a  second  count. 

829 


830      ADRENALIN,  ERYTHROCYTES  AND  LEUCOCYTES 


TABLE  I 


SvccBssivK  Leucocvtk  Counts  Following  thb  Injection  ok  i  Mg.  ok  Adrenalin 


Hours  after  Injection 


No. 

Control      yi           I          iH 

3 

3 

4 

S 

6 

7             8 

X 

1  Normal 

1    8,700 1  12,500 1  10,700 1  13.000 1 

11.700I 

16,600 1 

13.200 1 

II,IOO| 

13.000 

10,500 1  11,100 

3 

1  Normal 

1  13.900 1  17.900 1  19,5001  14,100 1 

13.900 1 

17,900 1 

16,300 1 

14,100 1 

12,200 

3 

1  Normal 

1    6,400 1    8.000 1    8.2001    6,200 1 

5.600 1 

6,000! 

1 

8,500 1 

4 

1  Normal 

1    6,800 1  12,800 1    6,900 1    7.300 1 

7.300 1 

8,900 1 

1 

7.600 1 

5 

Normal 

1     S.300I    7,500 1    6,100 1    5,200 1 

6.100 1 

5,800 1 

6,700 1 

6,700 1 

8,400 

8,700 1 

6 

Normal 

1    8,050  i  13,800 1    6.200 1    7.400 1 

8.iooi 

9.900 1 

1 

1 

7 

1  Normal 

1    8,40  o|    9,800 1  16,100 1  16,300 

13.200 1 

17,700 1 

12,300 1  16,000 1 

10,200 

1 

8 

IMumpa 

1     8,000 1  15,200 1    9.600 1    9.200 1 

8,100 1 

8,200 1 

1 

7,800 1 

9 

1  Influenza 

1    3.200I              1    3.OO0I              1 

3,900 1 

2,800 1 

1 

3.300 1 

10 

1  Influenza 

1  11.700I  23,2001  i2,900|  17.800I 

17,200 1 

II,900| 

I 

II.500I 

II 

1  Pneumonia 

1  14.500 1  15^400 1  17,800 1  13,800 1  15,600 1 

15.700 1 

12,600 1 

1 

14,600 

13,600 1 

la 

Pneumonia 

1    4.100I             1    5,6001             1 

4.700 1 

4,000 1 

4,000 1 

3.900 1 

4.100 1 

13 

Pneumonia 

1    5.600I  11,200|    4,8oo|    4.600I 

1 

1 

1 

1 

14 

Pneumonia 

1    7.  ioo|    7.200 1    5.300 1    3,400 1 

1.800 1 

2,500 1 

1 

1 

15 

1  Pneumonia 

1    3.000 1    3.200 1    3.400 1    3.200 1 

3.300  1 

3,300 1 

3,000 1 

1 

2,800 1 

1     3,700 

The  height  of  the  initial  rise  in  the  leucocytes  is  indicated  by  heavy  type. 


CASE  I.    TABLE  II 


Time 

Remakks 

Leuco- 
cytes 

v> 

ei 

a. 
§ 

i 

> 

s. 

> 

1 

V) 
H 
H 

X 
B. 

-J 

u 

0 

,3 

1 

i 

•< 

> 

\ 

i 

8 
7. 

I 

Atypical 
Lympuocy  t  ks 

Date 

H 

u 

M 

•< 

■< 

1 

xa-i6-i8 

6:00  P.M. 

Control 

9,400 1 57  5 

410 

42Sl 

1   OS 

10 

ia-17-18 

7aO  A.M. 

Control 

8,6oo|s2S 

OS 

37  5 

OS 

OS 

46-51 

1-0  1  4-0 

OS 

35 

Ea-i8-i8 

7^0 

Control 

9.600 1 53  5 

IS 

37  0 

IS 

10 

46-51 

1-5  1   IS 

30 

30 

1      8:10 

1      8,700 1 

1          1 

8:14 

Adrenalin 

1 

1          1 

8:50 

1    12,500 1 42  5 

40- S 

1   OS 

155-5 

3-5l   4-S 

90 

9:30 

10,700 1 68  0 

10 

31-0 

06 

39-5 

i-3l   3-0I 

I-0| 

3-3 

9:50 

13.000 1690 

30 

18  0 

10 

10 

|37-0 

3-0I   7-0 

i-6| 

10:30 

ii,70o|40  0 

21    0 

30 

30  0 

i-o|  4o{ 

30 

ii:30 

Dinner 

1 

1          1 

11:30 

16,600 1 64  0 

10 

33   0 

I-O 

50 

34  0 

I-Sl   30| 

3-0| 

1-0 

13:30   P.M. 

13.200  |68o 

23  S 

05 

10 

30  5 

o-sl   30| 

2-5l 

1-0 

1:20 

ll,loo|7l-5 

24  0 

37-5 

I'OJ     3-0| 

o-sl 

10 

3:30 

13.000  isso 

35   5 

0-S 

to 

41-5 

30|    I0| 

3-Sl 

1-0 

3:30 

1     10,500 149-5 

42-5 

0-5 

05 

48-5 

2-Sl   3-Sl 

oo| 

IS 

4:30 

11,1001460 

44-0 

1   OS 

Sl-0 

3-0|   3-Sl 

i-sl 

IS 

S:oo 

Supper 

1 

1           1 

S:30 

10,800 1 45  0 

45  0 

SO  0 

S-ol  3  o| 

3-0 

6:30 

9.600 1 18 -5 

7t-5 

74- S 

7-0I      1 

3-0| 

3-5 

7:20 

9.600 143-5 

OS 

44-5 

OS 

54-0 

30|   6-sl 

ADRENALIN,  ERYTHROCYTES  AND  LEUCOCYTES     831 


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Case  1. 


Case  II. 


CASE  II.    TABLE  III 


Time 

Remarks 

Leuco- 

CYTES 

s 

1 

i 

s 

8 
H 

1 

s 

1 

i 

5 
8 

Atypical 
Lymphocytes 

Date, 

H 

0 

1-1 

d 

1 

I-7-I9 

10:3s  A.M. 

Control             1    13.900 1 63 

10  32  s 

o.S 

3S 

IS 

IS 

OS 

10:3s 

Adrenalin          |               | 

11:03 

1    i3.8oo|4SSl  OSl43S 

1    0  SiSI           20 

OS 

6S 

11:33 

17.900I41SI    ISI46  S 

O-Sl    I-5|S6  S     10 

2   0 

3  0 

as 

ii:S3 

lO.SOOlso      1          I36 

1   4  01465     35 

OS 

60 

12:23   P-M. 

I4,IOO|70       1             |2I 

1    as  130      1 

6S 

" 

I2:S3 

i3.S)Oo|6i      1          I28  5 

1           1    IS|37S|    IS 

20 

40 

IS 

i:S3 

17.900ISS      1   0S|32  S 

2Sl  0  sUa-Sl   20 

SO 

IS 

OS 

3:10 

i6,30o|6S-5l          |22  5 

0  Si    10I29      1    2S 

40 

OS 

OS 

3:53 

1    14.100I66      1   0S|24S 

osl   0S|3I      1   2S 

as 

3  0 

4:53 

1    i3,aoo|6i      1          I39-5 

1   os|38      1    IS 

SO 

20 

OS 

CASE  IV.     TABLE  IV 

I-3-I9 

2:00  P.M. 

Control              1      6.800  ISOSI          I40S 

1       UosI 

2:00 

Adrenalin          |                III 

1          1          1 

2:30 

I    i2.8oo|s6     1          |25S 

osl          I46SI   10 

60 

OS 

los 

3:00 

1      6.900I61      1          I36S 

1             I380I    10 

10 

OS 

3:30 

1                            1      7.200|8r      1          |i2-5 

1           |I7SI    IS 

30 

OS 

IS 

4:00 

1      7.300I76      1          |23S 

1             13401 

OS 

S:oo 

1      8,900|69Sl          I28S 

1          I300I   OS 

IS 

1     7:00 

1      7.600I64     1          I340 

1             I340I    20 

832      ADRENALIN,  ERYTHROCYTES  AND  LEUCOCYTES 


Case  IV. 


All  cells  departing  from  the  normal  morphology  were  carefully  observed 
and  grouped  under  atypical  cells.  In  plotting  the  curves,  all  lymphocyte 
forms,  normal  and  atypical,  were  added  to- 
gether and  recorded  as  total  lymphocytes;  i 
m.  of  adrenalin  (i  c.c.  i-iooo  solution  P.D.) 
was  injected  intramuscularly  three  hours  after 
the  ingestion  of  food,  excepting  in  Case  XVII 
two  hours  after. 

The  Effect  oj  Adrenalin  on  the  Movement  of 
the  Leucocytes.  In  a  series  of  15  experiments. 
Table  I,  done  on  13  individuals,  made  up  of  5 
normals,  i  mumps,  2  influenzas,  and  5  influ- 
enza pneumonias,  there  was  a  rise  in  the 
leucocyte  curve  after  the  injection  in  12  in- 
stances. Case  IX,  which  did  not  react  with 
an  increase,  was  a  case  of  influenza  with  a 
distinct  leucopenia,  but  in  this  case  no  obser- 
vation was  made  one-half  hour  after  the  in- 
jection; the  other  was  a  case  of  influenza  pneu- 
monia. In  those  individuals  who  reacted  with 

a  rise  in  the  count,  the  height  of  the  reaction  was  reached  in  half  an  hour 
after  the  injection  in  7  instances,  in  an  hour  in  5  instances.  The  leucocyte 
increase  was  sustained  above  the  control  until  the  eighth  hour  in  i  (I), 

to  the  seventh  in  i  (V),  to  the  sixth 
in  I  (VII),  to  the  fifth  in  3  (II,  III, 
IV),  to  the  third  in  4  (VI,  VIII,  X, 
XI),  to  the  second  in  i  (XII)  and  to 
the  first  hour  in  i  (XIII). 

From  these  observations,  one  may 
conclude  that  an  intramuscular  in- 
jection of  I  mg.  of  adrenalin  causes 
an  increase  in  the  leucocyte  curve 
which  reaches  its  height  in  a  half  to 
one  hour  after  the  injection,  and 
returns  to  normal  or  to  the  control 
count  in  from  one  to  nine  hours.  It 
will  be  further  observed  that  a  very 
characteristic  occurrence  is  an  initial 
rise  and  decline  occupying  a  half  to 
i}4  hours,  subsequently  followed  by  a  second  rise  which  is  often  as  high 
as  and  sometimes  higher  than  the  initial  rise.  There  is  no  diff"erence  in  the 
reaction  when  it  occurs  in  normal  influenza  or  pneumonia  cases. 


1 

iJ 

jaa.k   1    i    i    1    i 

M 

&• 

iM- 

TBti 

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1 

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T 

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Case  V. 


ADRENALIN,  ERYTHROCYTES  AND  LEUCOCYTES      833 


CASE  V.  TABLE  V 


Time 

Rrmakks 

Leuco- 
cytes 

i 
1 

1 
i 

n 

s 

M 

U 

5 

I 

i 

1 

§ 

Atypical 
Lymphocytes 

Date 

1 

1 

a 

h 

I-3-I9 

7:40  P.M. 

Control 

S.300I46SI 

10I40.SI 

I.O 

3.0 

SI 

1-5 

45 

30 

10 

7:56 

Adrenalin 

1 

1 

8:i3 

S.800 147-8 

0-4I34-3 

0-4 

0-4 

49-5 

33 

7-9 

3-7 

3-8 

8:30 

7.SOOI300 

134-0 

10 

46  0 

40 

10 

30 

7-0 

8.56 

6.I00|S2S 

ao|33-o 

05 

10 

44-5 

10 

10 

6  S 

as 

9:a6 

S,aoo|49  0 

I360 

10 

10 

500 

10 

7-0 

3  0 

3-0 

9:56 

6,100 1 53-0 

134-5 

10 

05 

45-5 

10 

6  5 

30 

10:56 

S.800 1 54-0 

135-0 

30 

46  0 

80 

I-O 

1 1:56 

6.700 1 45  0 

I46-O 

a-0 

1-0 

SI  0 

10 

10 

ia:oo 

Cup  milk 

1 

1 

ia:s6  A.M. 

6,700 1 60  0 

I400 

40  0 

1:56 

8,400 1 65  0 

|a5-S 

I-O 

IS 

34  0 

1-0 

OS 

4-S 

x-o 

a:30 

7,100 1 59  0 

|38  0 

400 

10 

30 

3:00 

Orange 

1 

1 

3:56 

8,700  |s6o 

1400 

10 

430 

30 

10 

4:30 

Supper 

1 

1 

S:S6 

6,300  |s6o 

139-0 

OS 

OS 

435 

IS 

a-S 

6:so 

8,90o|6o-5 

134-S 

OS 

37-5 

1-5 

05 

3-0 

CASE  IX.  INFLUENZA.  TABLE  VI 


Date 


Time 


Remakks 


Leuco- 
cytes 


Atypical 
Lymphocytes 


3-3  6-18 


9:00  a.m.    iControl 

I  Adrenalin 


3,300  73-0 


37-0 


37-0 


1  10:00          1 

1     3.000 1 60  si 

I380I 

1          I39-0I 

1  io| 

1  11:00         1 

1      a,900|69Sl 

|300| 

1          |30  o|   0-5 

1           1 

1   i3:oo           1 

1      3,8oo|630| 

I370I 

1           |370|    I-O 

1          1 

1       1:00   PM.    1 

1       3.3OO|44-0| 

|S60| 

1           IS6-0I 

1           1 

CASE  X.    INFLUENZA.    TABLE  VII 


X-6-X9 

Hour 
After  inj. 

[Control 
Adrenalin 

11,700  177  oi 

l33-0| 

33-0  1 

1 

yi 

33,300 163  0| 

6 

0|39-0| 

l38o|   io| 

1  aoj 

I 

13,900 1 78  o| 

|330| 

laaol          1 

i>^ 

17.800I69  o| 

|3I-0| 

l3io|          1 

3 

17,300 1 75  o| 

laaol 

|as-o|         1 

1  3-o| 

5 

I1,SOO|730| 

|360| 

|a6o|          1 

834       ADRENALIN,  ERYTHROCYTES  AND  LEUCOCYTES 


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Case  XI. 


CASE  XI 

.     PNEUMONIA. 

TABLE  VIII 

Time 

RSHAKKS 

Leuco- 
cytes 

in 

< 
u 
ij 
u 

0 
0 

i. 

> 
0 

(U 

6 

'i 

PQ 

H 

> 

>< 

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Aytipical 
Lymph<kytes 

Date 

H 

5 

CO 

II 

1^ 

12-    -18 

8:30  A.M. 

Control 

14.S00I790I 

|2I 

9:00 

Adrenalin 

|730|   i.o|i4-5 

SSl    10I26 

45 

OS 

9:30 

IS,400|620|           |34Sl           1           |38 

OS 

OS 

2-5 

10:00 

I7.800|S70|           I430I           1           |43 

10:30 

i3,8oo|66-sl    i.o|20Sl   sol          |33S 

2-5 

4S 

11:00 

15.600I840I          |i6o|          1          |i6 

13:00 

iS.70o|74-o|          |i4-Sl    IS\  o-slas 

SS 

20 

I-O 

1:00    P.M. 

I3,6oo|88sl          |ii-o|          1          I11-5 

OS 

3:00 

i4,ioo|S70           I380I          1          |43 

10 

40 

S:oo 

13.600I610            |3S0|           1           |39 

10 

3  0 

CASE  XII.     PNEUMONIA 

TABLE  IX 

12-24-18 

9:00  A.M.  l(^ntrol 
lAdrenalin 

4,100  smear 

lost 

1 

10:00           1 

S.600  73     1 

I27 

1          |38 

i-o 

11:00           1 

4.700  sa     1 

I48 

1          I48 

12:00           1 

4.000  79     1 

1   7 

io| 

|i3-8 

so 

0-8 

1:00  P.M.  1 

4.000  76     1 

h4 

1             |34 

3:00           1 

3.900  |S2      1 

US 

1      I48 

S:oo           1 

4.100  |3S      1 

I65 

1          |6S 

ADRENALIN,  ERYTHROCYTES  AND  LEUCOCYTES      835 


CASE  XrV.     PNEUMONIA 

TABLE  X 

TiMB 

Remarks 

Leuco- 
cytes 

tn 

d 

0 

S 

1 

a, 

0 
a, 

pq 

>• 

X 
a. 

8 

X 

2 

< 

i 

H 

H 
>< 
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X 

1 

i 

X 
B. 

i 

Atypical 
Ly-mphocytes 

Date 

u 
0 

1 

1 

3 
5^ 

ia-30-18 

8:15  A.M.  1  Control 

3,100  580I         I430I         1 

42  0 

2:00  P.M.  1  Adrenalin 

1         1         1         1         1         1         1 

i 

2:30           1 

7,300|S90|             I390I    I0|            I40  0| 

1 

I-O 

3:00           1 

S,300|7IO|             |3S   0|    I0|             |38   0| 

20I 

10 

3:30           1 

3,400|S70|             I4IOI    I0|    IOI42   0| 

1 

4:00           1 

I,800|74-0|             |3I    0|    S-0|             |3I'0| 

S:oo            1 

2,500  1 69  0|             |37-0|    30|             I280I 

I-0| 

Tie  Degree  of  Leucocytosis.  The  increase  in  the  total  leucocyte  count 
varied  between  1500  and  11,500,  the  average  being  5000.  In  Case  I  the 
most  marked  rise  came  at  the  third  hour.  The  count  was  made  immediately 
after  dinner,  and,  for  that  reason,  we  have  not  included  it  in  the  above 
figures.  The  leucocyte  increases  are  all  outside  the  range  of  experimental 
error,  and  can  be  justly  attributed  to  the  action  of  the  adrenalin.  The 
average  increase  in  the  controls  is  4500,  in  the  pneumonias  3500.  The 
greatest  increase  observed,  11,500,  was  in  an  influenza  case.  It  will  be 
seen  that  no  increase  in  the  leucocytes  was  in- 
duced by  adrenalin  in  one  of  the  influenza  cases 
and  in  one  of  the  pneumonia  cases,  but  in  neither 
of  these  was  an  observation  made  during  the  first 
half  hour.  In  all  others  there  was  an  increase. 

The  Differential  Counts.  In  nine  of  the  series 
just  recorded,  diflFerential  counts  were  made  and 
have  been  arranged  in  the  accompanying  tables 
and  charts. 

The  Effect  on  the  Polymorphonuclears.  Follow- 
ing the  injection  of  adrenalin,  there  was  an  initial 
decrease  in  the  polymorphonuclears  in  2  cases 
(II  and  XI).  This  decrease  came  within  the  first 

half  hour  in  one  case,  a  quarter  of  an  hour  in  the  other.  In  each  case  there 
was  a  subsequent  rise  in  the  polymorphonuclears,  considerably  above  the 
control,  i}4  to  two  hours  after  the  injection.  One  of  these  cases  was  a 
normal  and  the  other  a  pneumonia.  There  was  an  initial  increase  in  the 
polymorphonuclears  in  4  cases  (IV,  V,  X,  XIV)  during  the  first  half  hour. 
No  counts  were  made  at  this  time  in  Cases  IX  and  X.  There  was  no 
change  during  the  first  half  hour  in  Case  I,  but  a  marked  rise  occurred  in 


Case  XIV. 


836      ADRENALIN,  ERYTHROCYTES  AND  LEUCOCYTES 

this  case,  at  one  and  at  i^  hours  after  the  injection.  After  the  initial  rise 
there  was  a  sudden  drop  in  the  polymorphonuclear  curve,  followed  by  a 
secondary  rise  in  four  cases  (I,  IV,  V,  X).  This  secondary  rise  reaches  its 
height  at  the  second  or  third  hour  in  all  cases  excepting  Case  V,  in  which 
it  was  delayed  until  the  sixth  hour.  In  those  cases  which  were  not  charac- 
terized by  an  initial  rise  in  the  polymorphonuclears  (I,  II,  XI)  the  sub- 
sequent rise  above  the  control  came  at,  practically,  the  same  time  as  the 
secondary  rise  in  the  first  group.  There  is  also  a  rise  at  this  time  in  Case 
XII,  in  which  the  control  differential  was  not  made.  There  was,  evidently, 
an  initial  rise  in  the  polymorphonuclears  in  this  case. 

The  Effect  on  the  Lymphocytes  or  Mononucleated  Cells.  There  is  an  initial 
increase  in  the  lymphocytes  in  6  cases  (I,  II,  IV,  V,  X,  XI)  within 
one-half  hour  after  the  injection  of  adrenalin.  Even  in  Case  IX  this  ten- 
dency of  the  lymphocytes  to  increase  immediately  after  the  injection  is 
shown.  This  initial  increase  in  the  lymphocytes  is  coincident  with  an 
increase  in  the  polymorphonuclears  in  3  of  these  cases  (IV,  V,  X). 
With  the  exception  of  Case  X  the  increase  is  relative;  in  this  case  the 
lymphocyte  increase  exceeds  that  of  the  polymorphonuclears.  In  3  cases 
(I,  II,  XI)  the  initial  lymphocyte  increase  is  coincident  with  a  declining 
or  stationary  polymorphonuclear  curve.  The  increase  in  the  lymphocytes 
is  followed  by  a  fall  as  abrupt  as  was  observed  in  the  rise.  This  is  often  far 
below  the  control  count.  The  fall  is  usually  observed  from  one  to  i}4  hours 
after  the  injection.  A  secondary  rise  always  takes  place  later  on,  returning 
to  the  control  count  in  from  four  to  five  hours.  In  one  instance,  a  reversal 
is  shown  in  the  differential  curves  at  this  time  (Case  I). 

Acidopbile  Granular^  Lymphocyte  Forms.  A  careful  account  was  made  of 
the  number  of  lymphocytes  showing  acidophile  granules  or  particles  in  the 
protoplasm.  Dr.  Calhoun  (4)  and  I  have  called  attention  to  the  increased 
number  of  these  cells  following  the  intravenous  injection  of  typhoid  protein 
in  arthritis  and  other  infections.  It  is  of  interest  to  note  that  of  the  9  cases 
of  this  series  in  which  systematic  differential  counts  were  made,  there  was 
an  increase  in  the  number  of  this  lymphocyte  form  in  6.  The  3  in  which 
none  of  these  cells  was  encountered  were  2  influenzas  and  i  pneumonia 
(IX,  X,  XII).  In  2  of  these  there  was  practically  no  leucocytic  resp)onse. 
In  Case  XIV  only  a  few  of  these  cells  appeared  after  the  injection,  but 
none  were  found  before  the  injection.'  In  only  i  of  the  other  6  cases  were 
they  found  in  the  control  in  the  same  percentage,  i  per  cent.  The  increase 

'  It  is  not  at  all  improbable  that  these  are  azure  granules  or  particles. 

•  It  is  interesting  to  note  that  two  days  later,  at  which  time  this  patient  was  given 
an  intravenous  injection  of  typhoid  protem,  this  acidophile  small  lymphocyte  appeared 
in  large  numbers  m  the  control,  16  per  cent,  and  increased  to  26  per  cent  one  hour  after 
the  injection.  This  was  the  second  day  of  her  pneumonia. 


ADRENALIN,  ERYTHROCYTES  AND  LEUCOCYTES      837 

varied  from  i  to  10  per  cent,  average  5  per  cent.  These  cells  appear  in  the 
greatest  numbers  one-half  hour  after  the  injection,  and  disappear  or  return 
to  the  per  cent  found  in  the  control  in  from  one  to  four  hours.  For  the  most 
part,  the  cases  showing  the  acidophile  particles  were  the  larger  type  of 
small  lymphocytes  with  pale  protoplasm.  They  are,  however,  also  en- 
countered in  the  small  lymphocyte  in  which  the  protoplasm  forms  only 
a  narrow  band  about  the  nucleus. 

The  Eosinopbiles.  Eosinophiles  were  increased  over  the  control  counts 
in  3  of  the  normal  cases.  In  Case  I,  1.5  per  cent  was  observed  in  the  control. 
At  the  ninth  hour  5  per  cent,  at  the  tenth  hour  7  per  cent,  one  hour  and 
twenty  minutes  after  supper.  Case  V,  control,  2.5  per  cent,  half  an  hour 
after  the  injection  4  per  cent.  Case  II,  control,  1.5  per  cent,  one  hour  after 
injection  3.5  per  cent.  There  was,  practically,  an  absence  of  eosinophile 
cells  before  and  after  the  injection  in  the  influenza  and  the  pneumonia 
cases. 

When  one  looks  at  the  tables  recording  the  differential  counts,  one  is 
impressed  with  the  simplicity  of  the  blood  picture  induced  by  the  adren- 
alin in  the  influenza  and  pneumonia  cases  as  compared  with  the  others, 
excepting  in  Case  XI,  where  most  of  the  cell  forms  are  represented. 

Discussion.  Hatigan*  (19 17)  observed  a  leucocytosis  following 
the  subcutaneous  injection  of  i  mg.  of  adrenalin.  He  found  in  the 
first  hour  after  the  injection  that  the  lymphocytes  were  markedly 
increased  and  that  they  decreased  the  second  hour,  during  which 
time  the  neutrophile  leucocytes  increased.  He  further  observed 
that  it  usually  took  six  hours  for  the  number  of  leucocytes  to  return 
to  normal,  and  that,  if  a  double  dose  were  given,  the  return  to  nor- 
mal was  proportionately  delayed.  Previous  to  Hatigan's  observa- 
tions, Castren  (5)  (191 6)  made,  practically,  the  same  observation,  a 
marked  increase  in  the  lymphocytes  and  a  less  pronounced  increase 
in  the  neutrophile  leucocytes  one-half  hour  after  the  injection  of 
I  mg.  adrenalin.  He  states  that  a  somewhat  similar  result  follows 
muscular  exercise. 

The  present  investigation  confirms  the  work  of  Castren  and 
Hatigan  in  that  it  shows  the  great  tendency  of  the  lymphocytes  to 
increase  after  the  injection  of  adrenalin.  It  further  shows  that  this 
increase  is  not  always  accompanied  by  a  decrease  in  the  jx)Iymor- 
phonuclears.  The  lymphocyte  increase  is  frequently  coincident  with 

*  Because  of  war  conditions  it  was  not  possible  to  secure  the  original  articles  of 
Hatigan  and  Castren. 


838      ADRENALIN,  ERYTHROCYTES  AND  LEUCOCYTES 

an  increase  in  the  polymorphonuclears,  and  at  such  a  time  the  in- 
crease is  usually  purely  relative.  When  the  increase  in  the  lympho- 
cytes is  coincident  with  a  decline  in  the  polymorphonuclear  curve, 
there  is  an  absolute  and,  sometimes,  marked  increase  in  the  lympho- 
cytes. This  increase  is  greater  than  the  loss  in  the  neutrophile  leu- 
cocytes. The  neutrophile  leucocyte  curve  almost  invariably  exhibits 
a  primary  and  secondary  rise.  The  secondary  rise  usually  begins 
between  the  first  and  second  hour,  and  reaches  its  height  at  the 
third  hour. 

The  acidophile  lymphocyte  is,  unquestionably,  increased  in 
numbers  following  the  injection  of  adrenalin.  There  seems  to  be 
no  definite  relationship  between  its  presence  and  that  of  the  eosino- 
phile.  When  the  eosinophile  cells  are  encountered  in  the  control  or 
after  adrenalin,  the  acidophile  lymphocyte  is  always  present,  but  it 
is  also  found  in  cases  in  which  no  eosinophils  are  found.  When 
the  eosinophile  lymphocyte  is  present  in  large  percentages,  the 
eosinophils  are  occasionally  also  present — in  Case  I,  9  and  7  per 
cent  respectively,  in  Case  V,  7  and  4  per  cent  respectively.  On  the 
other  hand,  the  highest  acidophile  lymphocyte  count,  10  per  cent, 
is  encountered  in  Case  IV,  where  the  highest  eosinophile  count  is  2 
per  cent.  The  significance  of  this  cell  has  not  yet  been  determined. 
We  (4)  have  expressed  an  opinion  that  they  are  due  either  to  some 
degenerative  process  or  that  they  are  present  in  response  to  some 
toxic  substance. 

The  Effect  oj  the  Adrenalin  on  the  Movement  of  the  Erythrocytes. 
Two  individuals  were  chosen  to  determine  the  eflfect  of  adrenalin 
on  the  red  blood  cells,  a  child  and  an  adult;  i  mg.  was  injected 
intramuscularly.  In  the  child.  Case  XVI,  the  counts  were  made 
every  half  hour  until  the  second  hour  and  every  hour  thereafter 
until  the  sixth  hour.  In  the  adult.  Case  XVII,  the  counts  were 
made  every  fifteen  minutes  until  the  second  hour  and  every  half 
hour  thereafter  until  the  third  hour.  Leucocyte  counts  were  also 
made.  While  the  same  general  changes  are  observed  in  each  experi- 
ment (see  Charts  XVI  and  XVII)  more  are  shown  when  the  counts 
are  made  at  fifteen-minute  intervals.  Two  control  counts  precede 
the  injection  in  each  experiment.  In  Case  XVII  there  is  an  abrupt 
rise  in  the  red-cell  curve  fifteen  minutes  after' the  injection.  This  rise 
reaches  its  height,  an  increase  of  944,000  cells,  thirty  minutes  after 


ADRENALIN,  ERYTHROCYTES  AND  LEUCOCYTES      839 

the  injection.  Then  comes  a  sudden  fall.  In  fifteen  minutes  the  count 
has  returned  to  normal,  but  its  downward  excursion  does  not  stop 
there;  it  continues  down,  and  in  fifteen  minutes  more  it  has  reached 
a  point  far  below  normal,  3,704,000.  This  entire  initial  phase  has 
occupied  only  one  hour.  The  curve  now  ascends  abruptly  to  near 
normal,  which  point  is  reached  in  fifteen  minutes. 


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Case  XVI. 


Case  XVII.     R,  upper  line,  red  cells;  O,  ratio 
between  reds  and  whites;  L,  leucocytes. 


A  secondary  rise  above  normal  takes  place  in  another  fifteen 
minutes,  i  >^  hours  from  the  time  of  the  injection,  and  at  2>^  hours 
it  has  reached  a  point  800,000  cells  above  the  control. 

From  these  observations  we  may  conclude  that  an  intramuscular 
injection  of  i  mg.  of  adrenalin  induces  an  abrupt  rise  in  the  erythro- 
cytes which  lasts  half  an  hour  and  is  followed  by  a  secondary  rise 
which  begins  \]/2  hours  after  the  injection  and  continues  as  long  as 
six  hours.  The  initial  rise  begins  very  promptly,  as  early  as  two 
minutes  after  the  injection. 


840      ADRENALIN,  ERYTHROCYTES  AND  LEUCOCYTES 

The  Mecbanism  by  wbicb  These  Blood  Changes  are  Brought  about. 
Changes  in  the  number  of  the  red  and  white  blood  corpuscles  per 
volume  of  blood  may  be  brought  about  experimentally  in  two  ways: 
(i)  By  methods  known  to  be  purely  mechanical;  (2)  by  methods 
which  stimulate  increased  cell  production. 

1 .  Mechanical  Methods.  The  simplest  of  these  is  the  local  change 
produced  by  the  elevation  of  an  extremity  which  may  lower  the 
red  blood  count  in  the  finger  or  toe  very  perceptibly.  Oliver  (6) 
has  shown  that  the  elevation  of  the  leg  for  fifteen  minutes  may  lower 
the  red  count  in  the  toe  14  per  cent  and  increase  it  in  the  finger  3  p>er 
cent  over  the  control  count.  Extraction  of  water  from  the  body  by 
sweating  and  diarrhea  raises  the  red  count,  as  do  many  diseases 
which  induce  these  two  conditions  (phthisis  and  cholera).  John  K. 
Mitchell  (7)  was  the  first  to  show  the  eff'ect  of  massage  on  the  blood. 
He  noted  an  immediate  rise  in  the  red  cells  following  massage. 
Ekgren  found  a  temporary  increase  in  the  leucocytes,  chiefly  in  the 
polymorphonuclears,  from  1000  to  7000.  In  a  case  of  pernicious 
anemia  in  Professor  Dock's  service  in  this  hospital  in  1898  I  made 
the  following  observations  on  the  effect  of  general  massage  on  the 
blood  cells  and  on  the  percentage  of  hemoglobin.  Table  XL  This 
report  has  some  interest  here  in  that  the  counts  were  made  not 
immediately  after  the  massage,  but  as  late  as  2^  hours  after.  In  18 
observations  it  will  be  seen  that  an  increase  in  the  red  cells  occurred 
in  a  large  per  cent  of  them.  The  increase  varied  from  100,000  to 
400,000  as  late  as  the  second  hour.^  Excepting  in  one  of  the  four 
observations  no  eff"ect  was  observed  on  the  leucocytes  as  late  as  one 
and  two  hours  after  the  injection. 

2.  Methods  which  Stimulate  Increased  Cell  Production.  It  has 
been  shown  (4)  that  the  intravenous  injection  of  foreign  protein  causes 
an  increase  in  all  members  of  the  white  cell  group  and  also  the  ap- 
p>earance  of  abnormal  cell  forms,  nucleated  reds,  and  myelocytes. 
We  have  attributed  these  changes  to  increased  histogenesis. 

Roth,  (9)  reviewing  and  repeating  the  work  of  Binz,  Wilkinson, 
Maurel,  and  Askenstedt,  on  the  effect  of  quinine  on  the  leucocytes, 
has  shown  that  after  ingestion  or  subcutaneous  injection  of  quinine 
in  animals  there  is  a  preliminary  increase  in  the  number  of  leu- 
cocytes in  the  first  half  hour.  At  this  time  there  is  a  relative  and  an 

"  Increases  below  100,000  might  be  within  the  range  of  experimental  error. 


ADRENALIN,  ERYTHROCYTES  AND  LEUCOCYTES       841 


absolute  increase  in  the  lymphocytes.  This  stage  is  followed  by  a 
leucopenia  which  lasts  for  several  hours,  when  a  secondary  leu- 
cocytosis  takes  place,  made  up  chiefly  of  polymorphonuclear  cells. 
The  same  reaction  was  noted  in  man,  but  to  a  less  marked  degree. 


TABLE  XI 


Effect  of  Massage  on  the  Red  Blood  Cells 

Date, 
1898 

Red  Cells 

BEFORE 

Massage 

Red  Cells 

Hemoglobin 

Time 

AFTER 

Massage 

Hr.   Min. 

Time 

Massage 

Given 

Min. 

Increase 
in  Red 
Cells 

Leucocytes 

AFTER 

Massage 

B*         A* 

Before 

After 

1-29 

1,164,800 

r. 176,000 

30          30 

I     00 

45 

11,200 

4.838 

14.006 

1-30 

1,262,400 

1,472,000 

30          35 

3     00 

30 

309,600 

7.639 

6.621 

a-  2 

1,267,200 

1,392,800 

30     1     30 

2     45 

IS 

35.600 

5.603 

7.38S 

a-  3 

i,32S,6oo 

1,313,600 

30     1     30 

3     35 

30 

6,780 

a-  5 

i,a33.7So 

1,408,000 

30     1     35 

3      00 

35 

174.250 

S.634 

a-  8 

i.S36,6oo 

i,7i6,s6o 

40     1 

I      00 

1          15 

179.960 

2-10 

1,822,400 

2,040,000 

40     1     40 

I     45 

IS 

317.600 

a-i2 

1,715,200 

1,798,400 

40      1     45 

I    50 

1          IS 

83.200 

a-is 

1,904,000 

1,910,400 

40      1 

3      00 

20 

6,400 

a-17 

1,800,000 

1,940,800 

45      1 

3      10 

30 

140,000 

1,888,000 

3     35 

2-31 

2,009.600 

2,118,400 

SO     1     55 

2      00 

IS 

108,000 

2-23 

a,i87,20O 

2,176,000 

50      1      SO 

1       3      15 

10 

2-24 

1,933,800 

2,100,800 

50      1      55 

I     45 

15 

168,000 

2-37 

2,137.600 

2,172,800 

50      1      55 

I     00 

1      30 

1        3S.300 

2,540,800 

1     60 

I     40 

403,300 

3-  I 

2,257,600 

2,288,000 

55      1      55 

I      00 

35 

30,400 

2,448,000 

1     60 

I     45 

190,400 

3-  4 

2,129,600 

2,232,800 

SO      1     55 

I     30 

20 

103.200 

3-13 

2,498,400 

3.590,400 

50      1 

2     00 

20 

93.000 

3-20 

2,441,600 

a,S5o,40o  1 

1     65 

I     30 

as 

108,800  1 

•  B, — before  massage.  A, — after  massage. 

Note  observation  on  Feb.  27.    Little  increase  at  i  hour,  marked  increase  at  i  hr.  40  minutes. 

Roth  isolated  the  spleen  and  confirmed  the  work  done  by  others, 
which  had  determined  that  quinine  given  subcutaneously  to  dogs 
brings  about  contraction  of  the  spleen.  He  then  studied  the  effect 
of  splenic  contraction  on  the  blood  cells  and  came  to  the  conclusion 
that  the  changes  induced  by  the  quinine  "may  be  due  to  mechan- 
ical forces  entirely,  namely,  the  contraction  of  the  organs  which  har- 
bor large  numbers  of  lymphocytes." 

Lamson  (lo)  and  Kieth  have  shown  that  epinephrin  causes  an 
increase  in  the  red  cells  per  volume  of  blood  in  animals.  They  seem 
to  have  shown  conclusively  that  this  increase  is  due  to  the  action 
of  the  epinephrin  on  the  liver,  for  when  they  excluded  the  liver  from 
the  general  circulation  the  injection  of  epinephrin  had  no  such  effect 
on  the  red  cells.  On  the  other  hand,  under  these  conditions  the  epi- 


842      ADRENALIN,  ERYTHROCYTES  AND  LEUCOCYTES 

nephrin  caused  a  decrease  in  the  plasma  volume  similar  to  that  in- 
duced by  sweating  and  diarrhea,  but  without  the  proportional 
increase  in  cells  that  accompanies  these  conditions.  This  observation 
lends  support  to  the  idea  that  a  proportional  number  of  corpuscles 
was  destroyed  or  driven  from  the  general  circulation.  Lamson  and 
Kieth  explain  this  phenomenon  on  the  grounds  that  epinephrin 
under  all  conditions  causes  a  decrease  in  the  plasma  volume  and 
when  the  liver  is  not  shut  off,  the  normal  flow  of  red  cells  into  the 
circulation  continues,  and  apparently  in  addition  to  this  the  dis- 
charge of  corpuscles  from  the  liver  is  increased,  as  the  reduction  of 
plasma  does  not  account  entirely  for  the  increased  count. 

One  might  argue  that  because  of  the  increase  in  the  red  cells 
the  increase  in  the  white  cells  is  relative  or  proportional.  In  Cases 
XVI  and  XVII  I  have  plotted  a  curve  on  the  graphic  chart  which 
shows  the  ratio  between  the  red  and  white  corpuscles.  The  base  line 
represents  the  ratio  in  the  control  counts.  In  Case  XVII  the  average 
ratio  in  the  control  counts  is  i  white  to  664  red  cells.  If  there  is  an 
actual  increase  in  the  number  of  white  cells  in  the  blood,  the  ratio 
at  the  time  of  the  increase  in  the  reds  should  be  low.  We  find  at 
9:30,  when  the  red  cells  reach  their  highest  point,  the  ratio  is  loWy 
i~475«  Putting  it  another  way,  at  this  time  if  the  control  ratio  is 
maintained  there  should  be  10,129  white  cells;  there  are  13,850, 
3721  more  than  there  should  be  on  this  hypothesis.  At  10:00,  when 
the  red  cells  reach  their  lowest  range,  there  should  be  6204  white 
cells.  This  is  practically  the  number  we  find.  In  both  experiments 
the  tendency  is  to  a  low  ratio  at  the  time  when  the  red  count  is  high. 

There  is  one  more  point  that  must  be  considered — the  prolonged 
eff'ect  of  the  adrenalin.  We  have  observed  this  eff"ect  not  only  on  the 
formed  elements  of  the  blood,  but  also  on  blood  sugar  curves  induced 
by  adrenalin  (i).  It  is  probable  that  a  hormone  action  is  responsible 
for  this  finding. 

In  Case  XVII  at  9:15  there  is  a  beginning  increase  in  the  red 
cells.  At  this  time  the  patient  was  shaking  hard,  her  hands  were 
cold,  stiff",  and  clammy.  The  blood  flowed  very  slowly  from  the 
finger.  At  9:30,  when  the  red  cells  reached  their  highest  p>oint,  these 
symptoms  were  less  marked,  and  the  blood  flowed  freely  from  the 
finger. 

From  these  observations,  it  appears  that  the  increase  in  the 


I 


DRENALIN,  ERYTHROCYTES  AND  LEUCOCYTES      843 

white  cells  following  adrenalin  is  not  entirely  proportional,  and 
must  be  due,  in  part,  to  the  discharge  into  the  circulation  of  extra 
numbers  of  leucocytes  from  the  cell  depots.  As  Lamson's  experi- 
ments show  that,  in  addition  to  the  increase  in  red  cells  that  would 
come  from  a  decrease  in  the  plasma  volume  by  the  adrenalin,  there 
is  an  overdischarge  of  red  cells  from  the  liver,  so  Roth's  experiments 
show  that  there  is  an  overdischarge  of  lymphocytes  from  the  spleen 
due  to  splenic  contraction. 

Since  we  know  that  adrenalin  similarly  contracts  the  spleen, 
that  the  white  cell  changes  after  adrenahn  are  practically  the  same 
as  those  produced  by  quinine,  and  that  the  red  cell  changes  are  the 
same  as  those  induced  by  massage,  one  feels  justified  in  concluding 
that  the  changes  in  the  blood  cells  induced  by  adrenalin  are  purely 
mechanical,  and  are  not  due  to  an  increased  histogenesis,  as  we 
believe  is  the  case  with  the  blood  changes  following  intravenous 
injection  of  typhoid  protein. 

Conclusions.  1 .  The  intramuscular  injection  of  i  mg.  of  adrenalin 
causes  an  increase  in  the  leucocytes.  There  is  an  initial  rise,  followed 
by  a  decline,  which  usually  takes  place  within  one-half  to  one  hour, 
a  secondary  increase  in  the  leucocytes  begins  at  the  second  hour  and 
may  continue  above  the  control  counts  until  the  eighth  hour.  A 
distinct  leucocytosis  is  often  induced. 

2.  There  is  a  distinct  tendency  for  the  lymphocytes  to  rise  very 
soon  after  the  injection.  This  increase  is  not  long  sustained.  The 
rise  is  usually  relative,  but  may  be  absolute,  and  it  is  usually  coinci- 
dent with  a  rise  in  the  polymorphonuclears.  A  secondary  rise  occurs, 
but  not  so  constantly  as  is  that  of  the  polymorphonuclears. 

3.  The  acidophile  lymphocyte  is  increased  in  numbers  after  the 
injection  of  adrenalin.  The  greatest  increase  usually  comes  one-half 
hour  after  the  injection. 

4.  Adrenalin  causes  an  abrupt  and  marked  rise  in  the  erythro- 
cytes during  the  first  half  hour.  At  the  end  of  this  time  they  may 
have  returned  to  normal.  A  secondary  rise  occurs  at  i>^  to  two 
hours  after  the  injection,  and  may  be  sustained  for  three  hours. 

5.  The  increase  in  the  red  cells  is  similar  to  the  increase  induced 
by  general  massage. 

6.  The  changes  in  the  blood  cells  induced  by  intramuscular 
injection  of  adrenalin  are  purely  mechanical  and  are  not  due  to  an 


844      ADRENALIN.  ERYTHROCYTES  AND  LEUCOCYTES 

increased  histogenesis,  as  we  believe  is  the  case  with  intravenous 
injection  of  typhoid  protein. 

BIBLIOGRAPHY 

1.  Cowie  and  Beaven,  "On  the  Clinical  Evidence  of  Involvement  of  the 

Adrenal  Glands  in  Influenza  and  Influenza  Pneumonia."  In  press. 

2.  Hatigan,  J.,  Wien.  klin.  Wcbnscbr.,  19 17,  XXX,    1541.  Ab.  Endocrin- 

ology, 1918,  p.  161. 

3.  Cowie  and  Beaven,  "Nonspecific  Protein  Therapy  (Typhoid  Protein) 

in  Influenza  Pneumonia,"  J.  Am.  M.  Ass.,  April  19,  1919,  11 17. 

4.  Cowie  and  Calhoun,  "Nonspecific  Protein  Therapy  in  Arthritis  and 

Infections,"  Arcb.  Int.  Med.,  Jan.  1919,  XXIII,  69-131. 

5.  Castren,  H.,   "Finska  Lakaresallskapets  Handlinger"    (Helsingfors) 

1916,  LVIII,  1605.  Ab.  Endocrinology,  I,  400. 

6.  Oliver,  Lancet,  1896,  I,  1778.  Quoted  by  Ewing,  "Clin.  Pathol,  of  the 

Blood,"  Sec.  Ed.,  1903. 

7.  Mitchell,  John  K.,  "The  Efi"ect  of  Massage  on  the  Number  and 

Hemoglobin  Content  of  the  Red  Blood  Cells,"  Am.  J.  Med  Sc, 
1894,  CVII,  502. 

8.  Ekgren,  Deutscbe  med.  Wcbnscbr.,  1902,  519.  Quoted  by  Ewing,  loc. 

cit. 

9.  Roth,  Geo.  B.,  "The  Action  of  Quinine  on  the  Leucocytes,"  J.  Pbar- 

macol.  &  Exper.  Tberap.,  1912-13,  IV,  157-165. 
10.  Lamson,  P.  D.,  Jr.,  Pbarmacol.  &"  Exper.  Tberap.,  1916,  VIII,  167  and 
130,  Lamson  and  Kieth,  ibid.,  247-251. 


STUDIES   ON   BLOOD    SUGAR 

effects  upon  the  blood  sugar  of  the  repeated 
indigestion  of  glucose 

By  Louis  Hamman 

IN  a  communication  to  the  Archives  oj  Internal  Medicine  Hamman 
and  Hirschmann(i)  have  demonstrated  the  blood-sugar  response 
to  the  ingestion  of  a  single  large  dose  of  glucose  in  normal 
persons  and  in  others  suffering  from  various  diseases.  For  this 
study  100  grams  of  glucose  were  administered  in  the  early  morning 
after  the  night  fast,  and  the  blood  sugar  and  urine  sugar  estimated 
at  short  intervals  thereafter.  It  was  demonstrated  that  there  are 
two  important  types  of  reaction,  the  normal  and  the  diabetic. 
There  is  still  a  third  type,  not  nearly  so  clearly  distinguished  as 
these  two,  the  reaction  of  increased  carbohydrate  tolerance.  Al- 
though the  reaction  in  normal  persons  varies  in  different  individuals 
and  in  the  same  individual  under  different  circumstances,  its 
general  characters  are  as  follows:  The  blood  sugar  rises  rapidly, 
but  seldom  exceeds  0.15  per  cent;  it  falls  somewhat  more  slowly 
to  the  original  level,  the  whole  reaction  being  over  in  less  than  two 
hours.  In  diabetics  the  rise  is  higher  and  longer  sustained.  If  the 
blood  sugar  surpasses  0.18  per  cent,  sugar  usually  appears  in  the 
urine,  but  sometimes  it  appears  at  a  somewhat  lower  level;  at  other 
times  it  fails  to  appear,  even  though  0.2  per  cent  of  blood  sugar  is 
exceeded.  From  two  to  five  hours  pass  before  the  blood  sugar 
reaches  the  original  fasting  level.  When  the  carbohydrate  tolerance 
is  increased,  there  is  only  an  insignificant  rise  in  the  blood  sugar, 
which  has  usually  a  low  fasting  level. 

Epstein  (2)  and  Woodyat  (3)  have  raised  the  objection  that 
these  variations  in  blood  sugar  following  the  ingestion  of  glucose 
represent,  not  real  variations  in  the  sugar  content  of  the  blood,  but 
apparent  variations  due  to  changing  blood  volume.  This  possibility 

845 


846  STUDIES  ON  BLOOD  SUGAR 

had  suggested  itself  to  us,  but  the  investigations  of  Mosenthal  and 
Hiller  (4)  show  conclusively  that  there  is  no  constant  relation 
between  variations  in  blood  sugar  percentage  and  the  water 
content  of  the  blood.  Indeed,  these  two  factors  show  such  bizarre 
relations  that  the  one  surely  cannot  depend  entirely  upon  the 
other. 

There  is  every  possible  gradation  in  the  response  to  glucose 
ingestion,  from  the  low,  insignificant  curve  of  high  glucose  tolerance 
to  the  extreme  and  prolonged  curve  obtained  in  severe  diabetes. 
However,  the  so-called  diabetic  curve  is  not  peculiar  to  diabetes, 
for  similar  curves,  though  usually  not  so  extreme,  are  obtained  with 
nephritis,  in  hyperthyroidism,  and  in  many  other  conditions  of 
lowered  carbohydrate  tolerance.  These  innumerable  gradations 
force  upon  us  the  conviction  that  disturbances  of  carbohydrate 
tolerance  are  quantitative,  not  qualitative,  variations.  In  other 
words,  that  diabetes  represents  functionally  a  disturbed,  not  an 
altered,  mechanism  of  carbohydrate  control. 

For  many  years  investigators  have  sought  to  distinguish  be- 
tween the  glycosuria  of  diabetes  and  the  glycosuria  due  to  a  great 
variety  of  other  conditions.  Of  the  many  distinguishing  marks  that 
have  been  proposed  only  two  (5)  are  still  urged  as  pertinent,  namely, 
the  parodoxical  law  of  Allen  and  the  diuretic  effect  of  sugar  in 
diabetes.  When  sugar  is  injected  intravenously  in  large  quantity 
it  acts  as  a  diuretic;  administered  otherwise,  it  diminishes  the  output 
of  urine.  In  diabetes  sugar  acts  as  a  diuretic  by  whatever  route  it 
be  administered.  While  this  distinction  is  true  between  normal 
and  totally  diabetic  animals,  it  is  only  relatively  true  in  human 
beings. 

The  ease  with  which  sugar  acts  as  a  diuretic  depends  upon  the 
degree  of  diabetes;  in  mild  cases  conditions  are  much  nearer  the 
normal  than  the  completely  diabetic.  In  other  words,  the  ease  with 
which  sugar  produces  diuresis  depends  directly  upon  the  degree 
of  carbohydrate  tolerance,  and  it  varies  with  this  tolerance.  Here 
again  the  distinction  is  purely  quantitative,  and  the  varying  diuretic 
effect  of  sugar  surely  cannot  be  pointed  out  as  a  mark  of  distinction 
between  diabetes  and  other  glycosurias.  How  convincingly  the 
observations  of  Woodyat  and  his  co-workers  (6)  confirm  this  state- 
ment! By  carefully  measured  and  timed  intravenous  injections  of 


STUDIES  ON  BLOOD  SUGAR  847 

glucose  the  tolerance  of  an  individual  can  be  accurately  deter- 
mined, and  sugar  begins  to  act  as  a  diuretic  when  this  limit  is 
overstepped. 

Therefore  the  only  remaining  feature  that  can  be  drawn  upon 
to  point  a  qualitative  distinction  between  diabetes  and  other  gly- 
cosurias is  Allen's  parodoxical  law.  Allen  (7)  enunciates  this  law 
in  these  words:  "Whereas  in  normal  individuals  the  more  sugar  is 
given  the  more  is  utilized,  the  reverse  is  true  in  diabetes."  Appar- 
ently this  law  was  enunciated  to  fit  conditions  in  totally  diabetic 
animals,  where  it  applies  aptly  enough,  but  if  we  properly  under- 
stand what  is  meant  by  the  law,  it  is  not  applicable  to  diabetes  in 
human  beings. 

When  carbohydrate  tolerance  is  only  mildly  reduced,  the  level 
of  tolerance  is  by  no  means  absolute.  For  instance,  if  the  ingestion 
of  50  grams  of  glucose  be  followed  by  the  excretion  of  i  gram  of 
glucose  in  the  urine,  it  does  not  follow  the  ingestion  of  100  grams 
will  cause  an  excretion  of  5 1  grams.  Far  from  it.  Such  experiments 
have  been  frequently  made,  and  but  a  small  proportion  of  the  excess 
is  recovered  from  the  urine.  Only  when  excessive  amounts  of  glucose 
are  administered  intravenously  and  at  a  uniform  rate  is  the  pro- 
portion of  excretion  constant.  Here,  again,  the  diflference  seems  dis- 
tinctly to  be  quantitative  and  not  qualitative.  It  occurred  to  me 
that  further  important  evidence  bearing  upon  this  point  could  be 
obtained  by  testing  the  reaction  of  patients  to  the  repeated  inges- 
tion of  glucose.  If  there  be  a  qualitative  diflference  in  the  utilization 
of  glucose  by  normal  persons  and  by  diabetics,  then  such  tests 
should  certainly  give  evidence  of  the  diflference.  The  only  observa- 
tions upon  this  point  that  I  was  able  to  find  in  the  literature  are  a 
few  experiments  upon  rabbits  reported  by  Bang.  In  normal  rabbits 
Bang  (8)  finds  that  the  second  administration  of  a  certain  dose  of 
glucose  given  during  the  decline  of  the  reaction  from  the  first 
administration  is  followed  by  a  much  less  marked  reaction  than 
was  the  first. 

Experimental  Results.  In  normal  persons  the  administration  of 
a  second  dose  of  glucose  immediately  after  the  reaction  to  the  first 
dose  produces  a  much  less  marked  reaction  upon  the  blood  sugar 
than  did  the  first  dose.  The  protocols  of  two  experiments  illustrate 
this. 


848 


STUDIES  ON  BLOOD  SUGAR 


Experiment    I.  E.  L.   C,   male,   single.  Age  twenty-eight.   Healthy 
physician. 


Time 

Blood  Sugar, 
Per  Cent 

Urine 
c.c.  per  Hour 

Urine  Sugar, 
Gm.  per  Hour 

8.30 

0086 
Glucose:     100  gm. 

in  300  c.c.  water. 

9.00                    1              0118             1                        88                  1                  0 

9.30                    1              0110             1                        74                  j                  0 

10.30 

0  087 
Glucose:     100  gm. 

162 
in  300  c.c.  water. 

0 

11.00                    1              0087             1                      150                  1                  0 

11.30                    1              0078             1                      150                  1                  0 

12.30 

0096 
Glucose:     100  gm. 

Ill 
in  300  c.c.  water. 

0 

1.00                    1              0080             1                        31                  1                  0 

1.30                    1              0087              1                        26                  1                  0 

2.30                    1              0094             1                        26                  1                  0 

Experiment  II.  B.  H.,  male,  single.  Age  twenty-nine.  Healthy  phy- 
sician. Patient  previously  tested  had  shown  a  low  renal  threshold;  that 
is,  sugar  had  appeared  in  the  urine  when  the  blood  sugar  reached  0.14 
per  cent. 


Time 

Blood  Sugar, 
Per  Cent 

Urine 
c.c.  PER  Hour 

Urine  Sugar, 
Gm.  PER  Hour 

9.15 

0.110 

28 

0 

9.16 

Glucose:     100  gm. 

in  300  c.c.  water. 

9.45 

0  162 

28 

trace 

10.15 

0  127 

30 

trace 

10.45 

0  130 

26 

0 

10.50 

Glucose:     100  gm. 

in  300  c.c.  water. 

11.20 

0  110 

28 

0 

11.50 

0  122 

21 

0 

12.20 

0  115 

26 

0 

These  experiments  indicate  that  the  mechanism  of  carbohydrate 
utilization,  once  stimulated,  works  more  efficiently  than  when  called 
upon  abruptly  to  manage  large  amounts  of  glucose.  Probably  to 
this  fact  is  largely  due  the  better  utilization  of  sugar  slowly  ab- 
sorbed, and  the  almost  unlimited  power  of  the  body  to  utilize 
starch. 

In  diabetics  the  same  difference  is  observed  as  in  normal  persons; 
the  following  protocols  illustrate  this,  although  >the  difference  is 
not  so  marked. 


STUDIES  ON  BLOOD  SUGAR 


849 


Experiment  III.  A.  B.,  male,  white,  married.  Age  forty-six.  Dis- 
pensary No.  46,750.  A  moderately  severe  diabetic  who  had  become  sugar- 
free  on  a  carbohydrate-free  diet. 


Time 

Blood  Sugar, 
Per  Cent 

Urine 
c.c.  PER  Hour 

Urine  Sugar, 
Gm.  per  Hour 

8.25 

0  161 

42 

0 

8.30 

Glucose:     20  gm. 

in  300  c.c.  water. 

9.00 

0205 

51 

0-3 

9.32 

0-244 

56 

1-57 

10.30 

0196 

45 

0  9 

11.30 

0  180 

68 

066 

11.35 

Glucose:     20  gm. 

in  300  c.c.  water. 

12.05 

0  161 

63 

0-23 

12.30 

0188 

55 

0  26 

1.30 

0-205 

117 

0-44 

2.30 

0-164 

113 

0-34 

Experiment  IV.  A.  T.,  male,  white,  married.  Age  forty.  Hospital 
No.  37,026.  Diagnosis:  Hyp>ertension,  myocardial  insufficiency,  emphysema, 
arteriosclerosis,  diabetes  mellitus,  obesity.  Patient  had  only  small  amount 
of  sugar  in  urine,  easily  controlled  by  moderate  regulation  of  diet. 


Time 

Blood  Sugar, 
Per  Cent 

Urine 
c.c.  PER  Hour 

Urine  Sugar, 
Gm.  PER  Hour 

8.35 

0150             1                          4 

0 

8.38 

Glucose:     100  gm.  |in  300  c.c.  water. 

9.10 

0-206             1                         5 

0 

9.42 

0-272             1                       33 

0-68 

10.45 

0-222             1                        76 

2-66 

11.15 

0-190             1                        49 

1-63 

11.18 

Glucose:     100  gm.  |in  300  c.c.  water. 

11.45 

0-212             1                       41 

1-36 

12.27 

0-209             1                       54                 1 

1-69 

12.57 

0-173             1                       37                 1 

0  56 

Persons  with  lowered  carbohydrate  tolerance,  but  not  out- 
spoken diabetes,  react  in  a  similar  way.  Even  if  the  second  dose 
of  glucose  be  much  larger  than  the  first,  the  reaction  following  is 
not  so  marked. 


Experiment  V.  W.  G.,  male,  white,  single.  Age  forty-seven.  Hos- 
pital No.  36,926.  The  patient  had  a  mild  infection  of  unknown  cause  and 
mental  symptoms.  No  definite  medical  diagnosis  made.  Sugar  never  found 
in  urine  on  ordinary  ward  diet. 


850 


STUDIES  ON  BLOOD  SUGAR 


Time 

Blood  Sugar, 
Per  CE^^• 

Urine 
c.c.  PER  Hour 

Urine  Sugar, 
Gm.  PER  Hour 

8.40 

0  120 

8-5 

0 

8.49 

Glucose:     50  gm.  in 

300  c.c.  water. 

9.20 

0  176 

314 

0 

9.53 

0-200 

463 

1-7 

10.55 

0166 

242 

0-8 

10.57 

Glucose:     50  gm.  in 

300  c.c.  water. 

11.30 

0  178 

246 

0-5 

12.00 

0  136 

132 

0  6 

12.45 

0  130 

79 

0 

Experiment  VI.  J.  H.,  male,  black,  married.  Age  thirty-nine.  Sur- 
gical No.  42,151.  Diagnosis:  Exophthalmic  goiter,  adenoma  of  thyroid.  No 
sugar  found  in  urine  on  usual  ward  diet. 


Time 

Blood  Sugar, 
Per  Cent 

Urine 
C.C,  per  Hour 

Urine  Sugar, 
Gm.  per  Hour 

8 

30 

0097 
Glucose:     100  gm.  in 

36 
300  c.c.  water. 

0 

9 

00 

0  130 

64 

0 

9 

30 

0  196 

31 

0 

10 

05 

0  177 

73 

0 

10 

45 

0  161 

49 

0 

11 

00 

Glucose:     100  gm.  in 

300  c.c.  water. 

11 

30 

0  173 

57 

0 

12 

00 

0164 

142 

0 

12 

30 

0  148 

1 

00 

0  116 

25                 1                 0 

Experiment  VII.  A.  N.,  male,  white,  married.  Age  thirty-seven.  Med- 
ical No.  36,828.  Diagnosis :  Bilateral  facial  palsy,  psychoneurosis.  No  sugar 
appeared  in  urine  on  ordinary  ward  diet. 


Time 

Blood  Sugar, 
Per  Cent 

Urine 
C.C.  PER  Hour 

Urine  Sugar, 
Gm.  per  Hour 

8 

25 

0093 

8 

30 

Glucose:     100  gm.  in 

300  c.c.  water. 

9 

00 

0  161 

32 

0 

9 

30 

0096 

97 

0 

10 

05 

0100 

129 

0 

10 

07 

Glucose:     150  gm.  in 

300  c.c.  water. 

10 

35 

0  148 

84 

0 

11 

05 

0097 

60 

0 

11 

36 

0094 

114 

0 

In  the  following  patient  the  utilization  of  glucose  is  normal, 


STUDIES  ON  BLCKDD  SUGAR 


851 


although  a  small  amount  of  sugar  appears  in  the  urine.  The  patient 
has  a  low  renal  threshold,  that  is  a  mild  grade  of  renal  diabetes. 

Experiment  VIII.  W.  A.  C,  male,  white,  married.  Age  thirty-six. 
Diagnosis :  Hyperthyroidism,  psychoneurosis,  renal  diabetes.  Small  amount 
of  sugar  occasionally  found  in  urine.  Considerable  sugar  in  urine  after 
ingestion  of  75  gm.  of  glucose. 


Time 

Blood  Sugar, 
Per  Cent 

Urine 
c.c.  PER  Hour 

Urine  Sugar, 
Gm.  per  Hour 

8.30 

0088 

43 

0 

8.40 

Glucose:     100  gm.  in 

300  c.c.  water. 

9.10 

0  125 

92 

trace 

9.35 

Glucose:     100  gm.  in 

300  c.c.  water. 

9.43 

0  105 

251 

02 

10.10 

0085 

658 

0 

10.50 

0084 

216 

0 

11.40 

0084 

68 

0 

It  was  found  in  testing  several  patients  that  they  reacted  to 
levulose  in  the  same  way  that  they  did  to  glucose,  only  the  blood 
sugar  rise  was  less  marked.  For  instance,  the  diabetic  whose  response 
to  glucose  is  detailed  in  Experiment  III  ^ave  the  following  response 
to  levulose: 

Experiment  IX.  A.  B.  Same  patient  as  in  Experiment  No.  III.  Male, 
white,  married.  Age  forty-six.  Dispensary  No.  46,750.  A  moderately  severe 
diabetic  who  had  t)ecome  sugar-free  on  a  carbohydrate-free  diet. 


Time 

Blood  Sugar, 
Per  Cent 

Urine 
CO.  PER  Hour 

Urine  Sugar, 
Gm.  PER  Hour 

8.30 

0167 

66 

0 

8.34 

Levulose:     20  gm.  in 

300  c.c.  water. 

9.01 

0177 

36 

0 

9.33 

0194 

68 

0-5 

10.32 

0177 

150 

0 

11.00 

0177 

329 

0 

11.02 

Levulose:     20  gm.  in 

300  c.c.  water. 

11.35 

0  167 

178 

0 

12.10 

0  184 

103 

0 

1.00 

0184 

144 

0 

Conclusions.  1.  The  ingestion  of  glucose  in  some  way  stimulates 
the  mechanism  of  carbohydrate  disposal  so  that  the  repeated 
ingestion  of  the  same  amount  causes  a  less  marked  hyperglycemia. 

2.  The  same  stimulating  effect  is  noted  in  diabetes;  the  second 


852  STUDIES  ON  BLOOD  SUGAR 

dose  is  followed  by  a  less  marked  hyperglycemia  and  glycosuria. 
However,  the  difference  between  the  effects  of  the  two  doses  is  less 
marked  than  in  normals,  and  varies  in  different  stages  of  the  disease. 
Perhaps  when  the  diabetes  is  very  severe  the  difference  may  com- 
pletely vanish. 

3.  In  renal  glycosuria  the  normal  stimulating  effect  of  the  in- 
gestion of  glucose  is  retained. 

4.  Levulose  produces  a  much  less  marked  hyperglycemia  and 
glycosuria  than  does  an  equal  amount  of  glucose. 

5.  The  difference  in  the  reaction  of  the  normal  and  the  diabetic 
is  a  quantitative,  not  a  qualitative,  diflference. 

BIBLIOGRAPHY 

1.  Hamman  and  Hirschman,  Arcb.  Int.  Med.,  1917,  XX,  761. 

2.  Epstein,  Discussion,  Soc.Jor  Clinical  Inves.,  May,  1916, 

3.  Woodyat,  Discussion,  Ass.  Am.  Pbys.,  May,  19 17. 

4.  Mosenthal  and  Hiller,  J.  Biol.  Cbem.,  1916,  XXVIII,  197. 

5.  Joslin,  "Treatment  of  Diabetes  Mellitus,"  2d  Edition,  1917. 

6.  Woodyat,  Sansum,  and  Wilder,  J.  Am.  M.  Ass.,  19 15,  LXV,  2067. 

7.  Allen,  "Glycosuria  and  Diabetes,"  1913,  Harvard  Univ.  Press. 

8.  Bang,  "Der  Blutzucker,"  Wiesbaden,  1913. 


INFLUENCE  OF  FAT  ON  CALCIUM    METABOLISM 
By  B.  Raymond  Hoobler,  M.D.,  Detroit,  Mich. 

(From  the  Laboratory  for  Medical  Research,  Children's  Free  Hospital,  Detroit,  Mich.) 

THERE  have  been  many  researches  conducted  in  recent  years 
which  have  demonstrated  that  calcium  metabolism  is  closely 
connected  with  the  functioning  of  the  nervous  system,  as  well 
as  being  of  prime  importance  in  the  up-building  of  the  bony  struc- 
tures of  the  body. 

A  negative  calcium  balance  cannot  long  exist  without  producing 
profound  changes  in  the  life  processes  of  the  individual.  When  such 
a  condition  exists  it  would  seem  a  very  easy  thing  to  change  a  nega- 
tive to  a  positive  balance  by  the  simple  procedure  of  administer- 
ing calcium  in  the  form  of  the  lactate  or  chloride,  but  such  adminis- 
tration is  not  always  accompanied  by  an  increase  in  the  retention  of 
calcium.  During  a  series  of  observations  on  infants  and  young  chil- 
dren it  was  found  that  the  absorption  and  retention  of  calcium  was 
markedly  affected  by  the  amount  and  kind  of  fat  in  the  diet  of  the 
individual  to  whom  the  calcium  was  administered. 

A  group  of  children  were  put  on  a  measured  diet,  and  their 
calcium  absorption  and  retention  were  obtained.  They  were  then 
continued  on  the  same  diet,  but  additional  fat  was  administered 
in  the  form  of  cod  liver  oil.  Each  child  showed  that  the  aggregate 
of  calcium,  both  absorbed  and  retained,  declined  to  the  extent  of  50 
per  cent  in  some  instances.  A  chart  is  submitted  showing  these 
results. 

This  observation  has  a  very  important  bearing  on  the  treatment 
of  rachitis  and  tetany,  many  clinicians  preferring  to  use  cod  liver  oil 
and  phosphorus.  It  would  seem  that  this  procedure  would  lessen 
calcium  retention  and  add  to  the  difficulty  rather  than  correct  it. 
A  further  interesting  observation  was  made  regarding  the  effect  on 
calcium  retention  of  a  diet  containing  quantities  of  milk  fat.  The 
results  of  such  observations  indicate  that  the  per  cent  both  of 
calcium  absorbed  and  retained  is  increased  as  the  milk  fat  in  the 
diet  is  increased.  Chart  II,  showing  absorption.  Chart  III  retention 

853 


854     INFLUENCE  OF  FAT  ON  CALCIUM  METABOLISM 


Tiflii!iiT:TT'riirii(Tir--rrni;'"'lpfi«^HinH4ffr 


4;i;;{  ji'Uf :;::;:.;-;  44:;:  j-l: -I  ;4i|:u:;;;  t:nir?-!'t?V 


Chart  I.  Effect  of  Odd  Liver  Oil  Medication  on  Calcium  Absorption  and  Retention 
%  Calcium  Absorption 


Chart  11.  Calcium  Absorption  on  High  and  Low  Fat  Diets 


INFLUENCE  OF  FAT  ON  CALCIUM  METABOLISM      855 

%  Calcium  Retained 


Chart  IV.     Effect  oi-  Low,  Medium  and  High  Fat  hoRMuuAs  on  the  Calcium 
Metabolism  of  Healthy  Infant 


856     INFLUENCE  OF  FAT  ON  CALCIUM  METABOLISM 

in  older  children,  and  Chart  IV  retention  in  infants.  This,  however, 
holds  only  in  those  individuals  who  do  not  develop  an  acidosis  on  high 
fat  feeding.  When  acidosis  does  develop  the  calcium  absorption  and 
retention  is  markedly  reduced,  as  is  whown  by  the  table. 


Period 

Fat  in 

FtX)D, 

Grams 

Calcium 

Ammonia 
in  Urine 

Acetone  and 

DiACETIC 

/S-oxybutyric 
Acid 

Per  Cent 
Absorbed 

Per  Cent 
Retained 

Abs. 
Amt. 

Per  Cent 
T.  Nit. 

Abs. 
Amt. 

Percent 
of  Urine 

Abs.       Per  Cent 
Amt.        of  Urine 

First 

70.04 

79.9   1      79.5 

0.26941        5.4 

.0          1    .0 

.2905         .392 

Second 

70.04 

79.9  1     79.7 

0.82321     18.6 

.278     1    .066 

.8625         .205 

Third 

70.04 

4.0  1       3.6 

1.55341     30.4 

.593     1    .078 

1.767           .232 

It  will  be  seen  that  calcium  absorption  fell  from  79.9  per  cent  to 
4  per  cent,  and  calcium  retention  fell  from  79.5  per  cent  to  3.6  per 
cent,  as  urinary  ammonia  increased  from  5.4  per  cent  to  30.4  per 
cent  of  total  nitrogen,  during  which  time  acetone  and  diacetic  acid 
increased  from  none  to  .593  gram,  and  /8-oxybutyric  acid  increased 
from  .2905  gram  to  1.767  grams  in  twenty-four  hours.  The  obser- 
vation was  discontinued  in  the  next  period  because  of  the  onset  of 
vomiting. 

Summary.  These  observations  indicate  (a)  that  cod  liver  oil  tends 
to  diminish  the  calcium  absorption  and  retention;  (6)  that  increasing 
quantities  of  milk  fat  tends  to  favor  calcium  absorption  and  reten- 
tion; (c)  that  the  last-named  observation  holds  true  only  as  long  as 
the  individual  does  not  develop  a  state  of  acidosis,  but  that  when 
acidosis  develops  calcium  absorption  and  retention  practically  cease. 


ON  CONTRA-LATERAL  REPRESENTATION  IN  THE 
CEREBRAL  CORTEX  OF  THE  PERIPHERAL 
BLOOD  VESSELS 

By  S.  p.  Kramer,  Cincinnati,  O. 

IN  May,  1909,*  while  removing  a  large  cortical  tumor  from  the 
left  rolandic  area,  it  was  noticed  that  the  radial  pulse  on  the 
contra-lateral  or  right  side  became  markedly  "weaker"  than 
that  on  the  left.  This  occurred  at  both  the  preliminary  and  final 
operations,  and  the  difference  in  the  two  pulses  was  evident  for  some 
hours  after  the  operative  procedures.  Since  then  I  have  had  an 
opportunity  to  record  a  similar  phenomenon  in  two  traumatic  cases 
involving  the  cerebral  cortex  in  which  there  was  a  measured 
difference  in  blood  pressure  (Riva  Rocci)  of  15  and  20  mm.  of  mer- 
cury. That  is,  the  blood  pressure  in  the  radial  artery  of  the  ex- 
tremity opposite  the  side  of  the  cortical  lesion  was  so  much  lower 
than  the  pressure  on  the  other  side. 

The  clinical  experiences  above  referred  to  called  for  an  investi- 
gation into  the  possible  changes  in  pressure  in  the  vessels  of  the 
extremities  as  the  result  of  stimulation  of  their  contra-lateral  cortical 
centers.  For  this  purpose  the  line  of  experiment  consisted  in  regis- 
tering the  changes  in  pressure  in  the  distal  end  of  the  divided 
femoral  artery.  The  artery  was  divided  well  below  the  profunda 
branch.  The  peripheral  pressure  recorded  there  varied  in  different 
animals  between  30  and  80  mm.  This  amount  of  pressure  probably 
depends  on  the  collateral  circulation,  but  it  was  a  priori  reasonable 
that  any  change  in  the  caliber  of  all  the  vessels  of  the  extremity 
below  the  point  of  ligature  would  manifest  itself  plainly  by  influ- 
encing the  pressure  as  measured  in  the  distal  end  of  the  divided 
artery.  Accordingly  the  leg  area  of  the  cortex  cerebri  on  both 
sides  was  stimulated  alternately  and  the  pressure  in  the  peripheral 
ends  of  both  femoral  arteries  was  recorded.  The  animals  were 
anesthetized  with  ether,  after  which  tracheotomy  was  performed 

*  N.  York  M.  J.,  Zenaer  and  Kramer,  October  2,  1909. 

857 


858  THE  PERIPHERAL  BLOOD  VESSELS 

and  ether  administered  through  the  tracheal  tube.  The  changes 
in  the  central  and  peripheral  blood  pressure  were  recorded  by 
mercury  manometers  connected  with  canulae  in  the  central  end  of 
carotid  artery  for  the  central  or  general  blood  pressure,  and  the 
distal  ends  of  the  divided  femoral  arteries  for  the  peripheral  pres- 
sure. The  femoral  canulae  were  always  placed  distal  to  the  giving  off 
of  the  profunda  branch.  In  some  experiments  changes  in  the  volume 
of  the  posterior  extremity  were  recorded  by  means  of  a  pleth- 
sphygmograph  connected  with  a  water  monometer.  The  cerebral 
cortex  was  stimulated  electrically  (faradic)  by  means  of  a  Kronecker 
coil  connected  with  platinum  electrodes  (bi-polar).  An  electric  signal 
placed  in  the  primary  circuit  registered  the  period  of  stimulation. 


■  ■ 


3 


-£ 


■^     ^- — - F 


Fig.  I.  Dog,  July  10,  1910. 

1.  Seconds.  2.  Period  and  Amount  of  Stimulation.  3.  Left  Peripheral  Pressure  (Fem- 
oral). 4.  Right  Peripheral  Pressure  (Femoral). 

On  stimulating  the  motor  area  of  the  cortex  of  a  dog  with  cur- 
rents of  moderate  intensity  and  with  light  anesthesia  the  general 
blood  pressure  as  measured  in  the  carotid  artery  showed  a  marked 
fall.  This  fall  comes  on  a  few  seconds  after  the  beginning  of  the 
irritation,  lasts  a  varying  period  after  the  cessation  of  the  stimu- 
lation, to  return  again  usually  inside  of  half  a  minute  to  the 
pressure  that  obtained  before  the  irritation.  This  fall  in  pressure 
may  be  preceded  by  a  momentary  rise,  very  slight  in  extent  and  not 
lasting  over  two  seconds.  If,  now,  the  anesthesia  be  deepened  by 
administering  more  ether,  this  effect  with  the  same  amount  of 
stimulation  does  not  occur.  Further,  if  the  electrodes  be  applied 
to  an  indiflFerent  part  of  the  cortex,  i.e.,  outside  the  motor  area, 
this  effect,  i.e.,  this  drop  in  blood  pressure,  does  not  manifest  itself. 

Fig.  I  is  a  tracing  in  which  the  record  is  given  of  an  experiment 
in  which  the  left  and  right  leg  areas  of  the  cerebral  cortex  were 


THE  PERIPHERAL  BLOOD  VESSELS  859 

alternately  stimulated  by  the  application  of  4000  Kronecker  units, 
while  the  peripheral  pressure  in  both  femoral  arteries  was  recorded. 
It  will  be  seen  by  referring  to  Fig.  i  that,  when  the  left  leg  area  in 
the  cortex  was  stimulated,  the  peripheral  blood  pressure  in  the 
right  femoral  artery  fell;  and  that  when  immediately  thereafter  the 
same  stimulus  was  applied  to  the  right  leg  area,  the  peripheral  pres- 
sure in  the  left  femoral  artery  fell. 

In  a  second  tracing.  Fig.  2,  the  circulatory  conditions  of  the 
whole  investigation  are  epitomized.  Here  three  manometers  were 


5. 


Fig.  2.  Dog,  August  3,  1910. 

1.  Seconds.  2.  Period  and  Amount  of  Stimulation  of  Left  Leg  Area  of  Cortex  Cere- 
bri. 3.  Central  Blood  Pressure  (Left  Carotid).  4.  Peripheral  Blood  Pressure  (Left  Fem- 
oral Artery).  5.  Peripheral  Blood  Pressure  (Right  Femoral  Artery). 

applied;  one  inserted  in  the  central  end  of  the  carotid  artery 
registered  the  general  blood  pressure.  The  other  two  were  con- 
nected with  the  distal  ends  of  the  divided  femoral  arteries.  A 
stimulus  of  4000  units  was  applied  to  the  left  cortical  leg  area. 
There  followed  a  marked  fall  in  the  general  blood  pressure  (pre- 
ceded by  a  slight  momentary  rise);  practically  no  change  in  the 
peripheral  pressure  in  the  left  femoral  artery,  and  a  marked  drop 
in  the  peripheral  pressure  in  the  right  femoral.  Now,  either  by 
gradually  increasing  the  anesthesia,  or  by  diminishing  the  amount 
of  stimulus,  one  can  arrive  at  a  degree  of  stimulation  which  will 
cause  the  drop  in  peripheral  pressure  on  the  contra-lateral  side  and 
leave  the  general  pressure  and  the  peripheral  pressure  on  the  homo- 
lateral side  unchanged.  This  is  shown  by  the  tracing  in  Fig.  2. 


86o  THE  PERIPHERAL  BLOOD  VESSELS 

These  results  are  independent  of  the  influence  of  muscle  contrac- 
tions, and  of  the  action  of  the  vagi  nerves,  for  they  are  obtained  in 
animals  that  are  curarized  and  after  section  of  the  vagi.  The  pre- 
liminary rise  spoken  of,  which  sometimes  precedes  the  fall  in  pres- 
sure, disappears  when  curare  is  given;  an  indication  that  this,  how- 
ever, is  due  to  the  direct  mechanical  pressure  of  the  contracting  muscles 
on  the  blood  vessels. 

That  the  fall  in  peripheral  pressure  is  due  to  a  true  dilatation  of 
the  vessels  of  the  extremity  is  supported  by  the  fact  that  it  can  be 

T     I    I  t    I    I    I    I     I    I     I    I    .1    I    I    I    I     I    I    I    I    I    t    I    I    t    I    I    I    I    I    I    I    I    I    I-  I    I     I    I    I     I    I    I    1 


^^''■i^  <i'<w> 


1iWWWy*«W«AM«JW«^^ 


Fig.  3.  Dog,  July  18,  1910. 

I.  Seconds.  2.  Period  and  Amount  of  Stimulation.  3.  Central  Blood  Pressure  (Left 
Carotid  Artery).  4.  Peripheral  Blood  Pressure  (Left  Temporal  Artery). 

produced  by  weak  stimulation  of  the  peripheral  end  of  the  divided 
sciatic  nerve.  (Shown  in  Fig.  3.)  The  injection  of  adrenalin  into 
the  femoral  artery  of  course  causes  a  rise  in  the  peripheral  pressure. 
The  experiments  described  above  were  done  in  the  laboratory 
of  my  lamented  friend  and  master.  Sir  Victor  Horsley,  during  the 
summer  of  19 10.  They  have  heretofore  not  been  published,  and  the 
original  manuscript  with  corrections  in  his  handwriting  is  one  of 
my  most  cherished  mementoes. 


COLLOID  CHEMISTRY  AND  MEDICINE 
By  Jacques  Loeb,  M.D.,  New  York 

(From  the  Laboratories  of  The  Rockefeller  Institute  for  Medical  Research) 

THE  development  of  medicine  and  biology  will  be  influenced 
to  a  considerable  extent  by  our  conception  of  the  nature  of 
the  reactions  between  crystalloids  and  colloids,  since  a  large 
part  of  the  reacting  material  of  the  body  is  colloidal.  The  only 
definition  of  colloids  which  does  not  go  beyond  the  facts  is,  as  far 
as  the  writer  is  aware,  that  colloids  cannot  diff'use  through  parch- 
ment (or  similar)  membranes,  which  are  permeable  for  crystalloids. 
It  is  assumed  by  many  that  the  laws  of  classical  chemistry  do  not 
apply  to  the  behavior  of  colloids;  and  those  who  hold  such  views 
call  themselves  "colloid  chemists."  This  school  by  no  means  in- 
cludes all  the  workers  on  colloids  or  proteins;  on  the  contrary, 
authorities  on  bio-colloids,  like  Hardy,  Sorensen,  Robertson,  and 
others,  take  the  opposite  view.  Since,  however,  colloid  chemists 
have  found  medicine  a  promising  field  for  propaganda,  it  may  seem 
pardonable  to  pass  in  review  some  of  their  methods  and  claims. 

The  writer  is  under  the  impression  that  this  new  development  of 
"colloid  chemistry"  was  largely  influenced  by  a  temporary  error 
into  which  Wilhelm  Ostwald  had  fallen,  namely,  that  atoms  and 
molecules  had  no  real  existence.  During  Ostwald's  period  of  war- 
fare against  "scientific  materialism"  some  of  his  followers  seized 
upon  the  colloids  as  the  means  of  creating  a  chemistry  free  from  the 
conception  of  the  real  existence  of  atoms  and  molecules.  Thus 
Freundlich  tried  to  show  that  the  interaction  between  colloids  and 
crystalloids  did  not  follow  the  law  of  mass  action,  but  a  diff'erent 
law,  his  so-called  adsorption  formula;  and  reactions  between  colloids 
and  crystalloids  were  not  supposed  to  occur  in  stoichiometrical 
relations;  it  was  also  claimed  that  solutions  of  colloids  were  not 
real  solutions,  and  that  the  osmotic  phenomena  observed  in  such 
solutions  could  not  be  explained  on  the  basis  of  classical  physical 

86i 


862  COLLOID  CHEMISTRY  AND  MEDICINE 

chemistry.  Notwithstanding  the  fact  that  the  complete  proof  of 
the  real  existence  of  atoms  and  molecules  has  abolished  the  justifi- 
cation of  the  dream  of  a  non-chemical  "colloid  chemistry,"  the 
movement  has  continued  to  spread. 

When  Ehrlich  appealed  to  Arrhenius  to  prove,  if  possible,  that 
the  phenomena  of  immunochemistry  were  chemical  in  character, 
Arrhenius  approached  the  problem  in  the  only  way  possible,  namely, 
from  the  viewpoint  of  the  law  of  mass  action.  He  could  show  that 
certain  reactions  in  immunochemistry  occurred  similarly  as  in  the 
interaction  between  a  weak  base  and  a  weak  acid,  (i)  Unfortunately 
his  investigation  brought  to  light  more  than  was  compatible  with 
Ehrlich's  side-chain  theory.  In  this  situation  Ehrlich  and  his  fol- 
lowers disavowed  classical  chemistry  and  accepted  the  escape 
ofiFered  by  "colloid  chemistry."  As  a  consequence  the  phenomena 
in  immunochemistry  are  to-day  frequently  discussed  in  terms  of 
adsorption.  As  long  as  these  discussions  are  based  upon  merely 
qualitative  experiments  or  consist  merely  in  assertions  that  the 
phenomena  in  question  are  "colloidal"  or  "adsorptive"  and  not 
chemical,  they  may  be  passed  over  as  verbalisms.  They  become 
worthy  of  consideration  when  they  are  quantitative  in  character, 
purporting  to  prove  that  the  phenomena  in  question  obey  the 
adsorption  formula  of  Freundlich  in  contradistinction  to  the  law 
of  chemical  mass  action.  In  this  connection  it  is  of  great  significance 
that  one  of  the  leading  physical  chemists  in  this  country,  Mr. 
Irving  Langmuir,  (2)  has  recently  investigated  the  adsorption  of  gases 
on  plane  surfaces  of  glass,  mica,  and  platinum,  where  the  purely 
chemical  character  of  the  forces  was  much  more  obscure  and  diffi- 
cult to  prove  than  in  the  case  of  the  reaction  between  electrolytes 
and  proteins.  He  was  able  to  show  that  "the  forces  causing  adsorp- 
tion are  typically  chemical,"  and  that  only  the  same  primary  and 
secondary  valence  forces  are  active  which  act  in  any  of  the  ordinary 
typical  chemical  reactions.  Stoichiometric  relations  only  fail  to 
hold  where  "steric  hindrance  efi'ects"  or  experimental  obstacles  and 
shortcomings  interfere.  As  far  as  Freundlich's  adsorption  equation 
is  concerned,  Langmuir  states  "that  it  agrees  very  poorly  with 
experiments  when  the  range  of  pressure  is  large."  Langmuir's 
investigations  leave  little  doubt  that  the  adsorption  formula  is 
only  the  result  of  accidental  experimental  difficulties.  Where  these 


COLLOID  CHEMISTRY  AND  MEDICINE  863 

difficulties  are  overcome  or  taken  into  due  consideration  the  laws 
of  classical  chemistry  seem  to  hold. 

II.  A  second  field  in  medicine  where  colloid  chemistry  has  made 
itself  felt  lies  in  the  discussion  of  the  exchange  of  water  between 
cells  and  the  surrounding  liquid — blood  or  lymph  in  animals  or  the 
sap  in  plants.  Whatever  special  conception  of  the  mechanism  of 
osmosis  may  be  held,  the  kinetic  theory  demands  that  the  osmotic 
pressure  be  determined  by  the  number  of  particles — molecules  or 
ions — in  solution  (or  suspension).  Thus  whenever  tissues  or  cells 
are  surrounded  by  membranes  which  are  permeable  to  water  but 
impermeable  to  either  salts  or  proteins  dissolved  or  suspended  in 
the  cell  sap,  a  diffusion  of  water  must  occur  until  osmotic  equi- 
librium is  established,  i.e.,  until  in  the  unit  of  time  as  many  molecules 
of  water  (and  of  other  substances  capable  of  diffusing  through  the 
membrane)  diffuse  into  the  cell  or  tissue  as  diffuse  out.  The  greater 
the  number  of  non-diffusible  molecules  or  particles  in  the  cell  the 
higher  the  hydrostatic  pressure  upon  the  cell  contents  must  become 
before  this  statistical  equilibrium  of  diffusion  is  established.  Since 
the  non-belief  in  the  existence  of  the  molecule  implied  also  a  non- 
belief  in  the  kinetic  theory  of  gases  and  liquids,  the  adherents  of  the 
system  of  "colloid  chemistry"  felt  obliged  to  look  for  an  explana- 
tion of  the  exchange  of  liquids  between  cells  and  their  surroundings 
on  a  basis  other  than  Avogadro's  and  van't  Hoff's  law.  Thus  as  late 
as  1 9 15  Wolfgang  Ostwald,  one  of  the  champions  of  a  non-chemical 
colloid  chemistry,  pubhshed  the  following  statement: 

"Recently  it  has  become  more  and  more  clear  that  such  membranes 
and  the  corresponding  osmotic  processes  are  much  rarer  than  had  been 
assumed  and  that  they  occur  only  in  limited  cases,  e.g.,  plant  cells  or 
animal  eggs,  but  that  they  cannot  solve  the  whole  problem.  It  has  become 
manifest  especially  by  the  investigations  of  Martin  H.  Fischer,  that 
the  water-binding  properties  of  the  colloids  and  not  of  the  molecular  con- 
stituents of  organized  matter  play  the  main  r6Ie  in  the  binding  and 
movement  of  water.  We  are  dealing  chiefly  with  phenomena  of  hydration 
(swelling)  and  dehydration,  such  as  we  can  also  observe  in  gelatin  plates 
or  other  dried  material.  "(3) 

The  writer  is  not  aware  that  Fischer  has  demonstrated  any  such 
thing  as  claimed  by  Ostwald.  Fischer  (4)  merely  asserts,  without 
giving  any  proof,  that  the  swelling  of  muscle  in  distilled  water  is  not 


864  COLLOID  CHEMISTRY  AND  MEDICINE 

due  to  a  difference  of  the  osmotic  pressure  of  the  solution  of  salts 
and  proteins  in  the  muscle  and  the  surrounding  water,  but  to  the 
following  hypothetical  conditions,  namely,  that  in  the  muscle  acids 
jare  present  which  tend  to  cause  a  swelling  of  the  colloids  of  the 
muscle.  This  swelling  he  furthermore  supposes  to  be  prevented 
by  the  presence  of  salts.  When,  however,  the  muscle  is  put  into 
distilled  water,  he  assumes  that  the  salts  diffuse  out  of  the  muscle, 
thereby  removing  the  obstacle  to  the  swelling  influence  of  the  acid. 
This  he  conceives  to  be  the  cause  of  the  swelling  of  the  muscle  in 
distilled  water.  He  has  not  furnished  any  of  the  data  necessary  to 
even  test  his  assumption,  viz.,  the  determination  of  the  pH  in  the 
muscle  cells;  of  the  isoelectric  points  of  the  proteins  in  the  muscle; 
of  the  nature  and  concentration  of  the  salts  in  the  muscle;  of  the 
rapidity  at  which  they  diffuse  out  of  the  muscle.  These  data  must 
be  on  hand  before  Fischer's  claims  can  be  taken  into  consideration. 
Long  before  191 5  it  was  known  that  the  exchange  of  water 
between  muscle  and  surrounding  solution  is  actually  determined 
by  the  laws  of  classical  physical  chemistry.  Through  the  older  experi- 
ments of  Nasse  and  the  writer  (5)  it  had  been  shown  that  in  neutral 
solutions  of  salts  the  gastrocnemius  of  a  frog  neither  loses  nor  takes 
up  water  when  the  osmotic  pressure  of  the  salt  solution  is  equal 
to  that  of  a  one-eighth  gram-molecular  solution  of  NaCI,  regardless 
of  the  nature  of  the  salt;  and  if  the  concentration  of  the  salt  is 
slightly  higher  the  muscle  loses,  when  the  concentration  is  slightly 
lower  it  takes  up  water.  If  van't  Hoff's  law  holds  for  the  exchange 
of  water  between  the  muscle  and  the  surrounding  fluid  we  should 
be  able  to  calculate  exactly  the  molecular  concentration  of  a  sugar 
solution  at  which  the  muscle  should  neither  take  up  nor  lose  water, 
namely,  it  should  be  that  concentration  of  sugar  which  has  the  same 
number  of  particles  in  the  unit  of  volume  as  an  M/8  NaCI  solution. 
This  calculated  value  is  for  sugar  0.231  gram-molecular.  If,  however, 
the  exchange  of  water  is  determined  in  the  way  suggested  by  Fischer 
and  endorsed  by  Ostwald,  the  muscle  must  swell  in  any  concentra- 
tion of  sugar,  since  sugar  can  have  no  antagonistic  action  upon  the 
hypothetical  swelling  effect  of  the  hypothetical  acid  in  the  muscle.* 
It  has  been  demonstrated  by  Overton,  (6)  Hober,  (7)  and  a  number  of 

^ '  This  antagonistic  effect  of  a  salt  is  said  to  be  due  to  the  repression  of  the  electrolytic 
dissociation  of  the  protein  salt,  on  account  of  the  common  anion.  Sugar,  not  being  an 
electrolyte,  can  have  no  such  repressing  effect. 


COLLOID  CHEMISTRY  AND  MEDICINE  865 

other  workers,  that  the  gastrocnemius  of  a  frog  neither  loses  nor 
takes  up  water  when  the  concentration  of  the  sugar  is  what  it  should 
be  if  the  law  of  van't  HoflF  holds  for  the  adsorption  of  water  by  the 
muscle,  namely  about  0.231  gram-molecular.  Moreover,  it  can  easily 
be  shown  that  the  muscle  takes  up  water  when  the  molecular  con- 
centration of  the  sugar  is  only  slightly  lower  than  0.231  M  and 
that  the  muscle  loses  water  when  the  concentration  of  the  sugar 
is  only  slightly  higher  than  0.231  M. 

"[This  was  confirmed  for  three  sugars,]  a  mono-saccharide,  grape  sugar;  a 
disaccharide,  cane  sugar;  and  a  trisaccharide,  raffinose.  The  following  table 
gives  the  change  in  weight  of  the  muscle  [in  per  cent  of  the  original  weight 
of  the  latter]  in  these  solutions  in  one  hour,  [the  plus  sign  indicating  a 
gain,  the  minus  sign  a  loss  in  weight  on  the  part  of  the  muscle.] 


0-2  M 

0-25  M 

0-35  M 

Grape  sugar 

Per  Cent 
+2-9 

Per  Cent 
-1-6 

Per  Cent 

-7-7 

Cane  sugar 

+3.8 

-1-2 

-61 

Raflinose 

+1-7 

-3-3 

-8-9 

"The  turning  point  between  loss  and  gain  of  weight  lies  for  all  three 
sugars  between  the  same  limit  of  molecular  concentration,  namely,  between 
0.2  and  0.25  M;  and  the  most  important  fact  is  that  the  value  for  all 
three  different  sugars  lies  between  the  limits  calculated  on  the  assumption 
that  the  exchange  of  water  between  muscle  and  surrounding  solution  is 
determined  by  the  Avogadro-van't  Hoff  law. "(8) 

We  may  therefore  feel  certain  that  the  laws  of  classical  physical 
chemistry  account  for  the  exchange  of  water  between  striated  muscle 
and  the  surrounding  liquid  and  that  the  vague  speculations  of  Ost- 
wald  and  other  colloid  chemists  are  untenable. 

III.  The  behavior  of  gelatin,  especially  the  swelling  of  gelatin 
plates,  has  served  as  a  basis  for  many  attempts  at  explaining  life 
phenomena.  Hofmeister  (9)  compared  the  amount  of  swelling  of  gela- 
tin plates  in  solutions  of  different  salts  and  stated  that  the  salts, 
according  to  their  effects  upon  swelling,  may  be  divided  into  two 
groups.  The  one  group  makes  gelatin  plates  swell  more  than  they 
do  in  distilled  water;  the  other  makes  them  swell  less.  The  former 
group  includes  NaBr,  NaNOs,  NH4CI,  NaCl,  KCl,  while  the  "de- 
hydrating" group  includes  the  acetates,  citrates,  tartrates,  and 
sulphates.  From  these  observations  colloid  chemists  have  concluded 


866  COLLOID  CHEMISTRY  AND  MEDICINE 

that  it  is  chiefly  the  anion  which  decides  the  swelling,  CI,  Br,  NOs 
having  a  hydrating,  while  acetates,  sulphates,  citrates,  and  tar- 
trates have  a  dehydrating  eff'ect.  Hofmeister  used  rather  high  con- 
centrations of  the  salts,  and  the  eff'ects  which  he  observed  were  very 
small,  so  small,  indeed,  that  the  writer  when  he  recently  read  Hof- 
meister's  paper  thought  he  had  by  mistake  gotten  hold  of  the  wrong 
publication.  Ralph  S.  Lillie  (lo)  later  claimed  to  have  confirmed  Hof- 
meister's  statement  on  the  relative  efficiency  of  the  anions  in 
studying  the  efi"ects  of  these  salts  on  the  osmotic  pressure  of  gelatin 
solutions.  It  is  also  generally  assumed  that  both  oppositely  charged 
ions  of  a  neutral  salt  aflfect  the  swelling,  acting,  however,  in  an  op- 
p)osite  sense,  the  anion  being  in  general  more  efficient  than  the 
cation.  These  statements  are  no  longer  tenable,  owing  to  the  fact 
that  in  all  these  experiments  two  serious  errors  were  made:  first, 
the  effect  of  the  electrolyte  upon  the  gelatin  was  always  measured 
in  the  presence  of  the  electrolyte,  and  second,  the  hydrogen  ion 
concentration  of  the  solution,  in  which  the  gelatin  was,  was  not 
measured.  In  avoiding  these  errors  the  writer  found  that  the  effects 
of  the  anion  claimed  by  Hofmeister  and  the  colloid  chemists  do  not 
exist,  and  that  under  the  conditions  under  which  Hofmeister's  and 
Lillie's  experiments  were  made  the  anion  of  a  neutral  salt  cannot 
affect  the  gelatin,  (ii) 

The  writer's  experiments  have  led  to  the  result  that  the  behavior 
of  gelatin  (and  probably  of  all  proteins)  is  easily  understood  if  we 
consider  it  as  an  amphoteric  electrolyte  which  obeys  the  laws  of 
classical  chemistry.  Amphoteric  electrolytes  are  characterized  by 
the  fact  that  they  are  capable  of  attaching  an  acid  as  well  as  an 
alkali.  Whether  they  do  the  one  or  the  other  depends  on  the  hydro- 
gen ion  concentration  of  the  surrounding  solution.  When  this 
hydrogen  ion  concentration  exceeds  a  critical  value — which  is 
called  the  isoelectric  point  of  the  protein — the  latter  will  attach 
acid  molecules  and  form  a  salt,  dissociating  electrolytically  into  a 
complex  protein  cation  (containing  the  H  ion  of  the  acid)  and  an 
anion,  that  of  the  acid  used,  e.g.,  HBr  or  HCl.  Such  gelatin  hydro- 
bromide  or  hydrochloride  can  exchange  its  anion  with  the  anions 
of  neutral  salts,  but  is  not  affected  by  the  cations  of  these  salts, 
contrary  to  the  assumptions  current  in  colloid  chemistry. 

When  the  hydrogen  ion  concentration  is  lower  than  that  defining 


COLLOID  CHEMISTRY  AND  MEDICINE  867 

the  isoelectric  point  the  protein  is  capable  of  combining  only  with 
alkalies  forming  metal  proteinates  which  dissociate  electrolytically 
into  a  positive  metal  and  a  negative  gelatin  ion.  Such  metal  protein- 
ates can  exchange  only  their  metal  ions  with  those  of  neutral  salts, 
but  they  are  not  affected  by  the  anions  of  neutral  salts.  Since 
common  gelatin  solutions  have  generally  a  hydrogen  ion  concen- 
tration lower  than  that  of  the  isoelectric  point  of  gelatin,  such  gela- 
tin cannot  be  affected  by  the  anions  of  a  neutral  salt,  as  is  claimed 
in  colloid  chemistry. 

At  the  isoelectric  point  the  gelatin  is  practically  neither  capable 
of  electrolytic  dissociation  nor  capable  of  reacting  with  neutral 
salts,  and  hence  it  is  affected  by  neither  anion  nor  cation  of  a  neu- 
tral salt.  At  the  isoelectric  point  the  gelatin  exists  as  pure  gelatin, 
i.e.,  gelatin  free  from  ionogenic  impurities. 

These  statements  on  gelatin  are  based  on  volumetric  analyses. 
The  isoelectric  point  of  gelatin  was  found  by  Michaelis  (12)  with  the 
aid  of  migration  experiments  in  the  electric  field  to  lie  at  pH  =  4.7. 
The  writer's  experiments  have  shown  that  the  more  the  pH  exceeds 
4.7  the  more  of  the  gelatin  exists  in  the  form  of  metal  gelatinate. 
When  pH  <  4.7,  i.e.,  when  gelatin  is  on  the  acid  side  of  its  iso- 
electric point,  the  lower  the  pH  the  more  gelatin  exists  as  gelatin 
chloride  (if  the  acid  used  was  HCI).  The  limit  is  reached  in  both 
directions  when  all  the  gelatin  is  transformed  into  metal  gelatinate 
or  gelatin  chloride  respectively. 

For  a  qualitative  demonstration  of  these  facts  we  can  treat 
gelatin  with  silver  salts,  copper  salts,  dyes,  etc.,  which  modify  the 
color  of  the  gelatin,  while  for  volumetric  analyses  we  may  treat  gela- 
tin with  salts  of  Ag,  Br,  CI,  CNS;  the  amount  of  these  ions  in  combina- 
tion with  gelatin  can  be  determined  by  the  methods  of  Volhard. 

Fig.  I  gives  a  demonstration  of  the  fact  that  silver  gelatinate 
can  only  exist  on  the  more  alkaline  side  from  the  isoelectric  point 
of  gelatin  (pH  =  4.7).  One  gram  of  finely  powdered  commercial 
Cooper's  gelatin  is  put  for  one  hour  at  20°  into  each  of  a  series  of 
beakers  containing  100  c.c.  of  M/16  silver  nitrate  solution.  Cooper's 
gelatin  is  impure,  consisting  mainly  of  calcium  gelatinate  and  pos- 
sessing a  pH  of  about  7.0.  In  the  beakers  containing  the  AgNOj 
solution  the  calcium  gelatinate  is  transformed  into  silver  gelatinate. 
The  gelatin  of  each  beaker  is  then  put  into  a  cylindrical  funnel, 


868  COLLOID  CHEMISTRY  AND  MEDICINE 

the  AgNOs  solution  is  allowed  to  drain  off,  and  more  or  most  of  the 
excess  of  free  AgNOa  left  in  the  capillary  spaces  between  the 
granules  of  gelatin  is  removed  by  two  or  more  washings  with  25  c.c. 
H2O  each.  Then  the  gelatin  in  the  different  funnels  is  brought  to  a 
different  pH  by  perfusing  each  funnel  three  times  with  25  c.c.  of  a 
solution  of  HNO3,  the  concentration  of  which  was  different  for  each 
funnel.  Then  the  excess  of  the  acid  is  washed  oflf  by  four  perfusions 
with  distilled  water.  Since  all  the  funnels  have  the  same  diameter 
the  height  of  the  column  of  gelatin  after  all  the  liquid  has  drained 
off  serves  as  a  measure  of  the  degree  of  swelling.  The  gelatin  is  then 
made  into  a  i  per  cent  solution  and  put  for  20  hours  into  collodion 
bags  to  measure  the  osmotic  pressure.  Each  collodion  bag  is  sur- 
rounded by  400  c.c.  distilled  water.  This  allows  the  further  removal 
by  dialysis  of  any  traces  of  free  silver  nitrate  that  may  still  have 
been  left.  All  this  is  done  in  the  dark  room.  The  next  day  the  height 
of  the  column  of  solution  in  the  manometer  is  measured,  the  pH 
of  each  gelatin  solution  ascertained,  and  the  quantity  of  Ag  in  25  c.c. 
I  per  cent  gelatin  solution  is  determined  by  Volhard's  method. 
Twenty  c.c.  of  each  gelatin  solution  are  put  into  test  tubes  and 
exposed  to  the  light.  It  is  found  (Fig.  i)  that  all  tubes  containing 
gelatin  with  a  pH  >  4.7  turn  black  in  a  few  hours,  while  all  the 
tubes  containing  gelatin  with  a  pH  <  4.7  show  no  trace  of  darkening 
even  when  exposed  to  the  light  for  weeks.  The  photograph  (Fig.  i) 
was  taken  after  an  exposure  to  the  light  (often  direct  sunlight) 
for  three  weeks.  It  is,  therefore,  obvious  that  the  silver  gelatinate 
originally  formed  could  only  continue  to  exist  for  pH  >  4.7,  i.e., 
on  the  alkaline  side  of  the  isoelectric  point.  A  similar  demonstra- 
tion can  be  given  when  we  substitute  for  the  treatment  with 
silver  nitrate  a  treatment  with  neutral  red  or  copper  acetate,  etc. 

At  the  isoelectric  point  (pH  =  4.7)  the  gelatin  is  insoluble  and 
held  in  fine  suspension.  This  is  indicated  by  the  fact  that  at  this 
point  the  solution  is  opaque,  while  for  pH  <  4.7  the  gelatin  is  the 
more  soluble  the  more  the  pH  differs  from  4.7. 

If  we  return  to  our  experiment  it  can  be  shown  that  in  the  non- 
blackened  test  tubes,  i.e.,  on  the  acid  side  of  the  isoelectric  point, 
the  gelatin  existed  in  the  form  of  gelatin  nitrate.  This  can  be  proved 
by  the  fact  that  if  we  bring  the  gelatin  in  different  funnels  to  a 
different  pH  by  treating  it  with  a  different  concentration  of  HNO» 


pH   3.7 


Fig.  I.  Photograph  of  Gelatin  Treated  with  Silver  Nitrate. 

Each  Test  Tube  Contains  a  i  per  cent  Solution  of  Gelatin  Which  Had  Previously 
Been  Treated  with  M/16  Silver  Nitrate,  but  was  Brought  afterwards  to  a  Different 
pH  by  Treating  it  with  HNO3  of  Different  Concentrations  and  by  Removing  the  Excess 
of  Acid  and  01  Silver  Nitrate  by  Washing  and  Dialysis. 

When  these  test  tubes  were  exposed  to  light,  all  the  gelatin  with  a  pH  >  4.8  turned  black  in  a  few 
hours,  while  none  of  the  test  tubes  containing  gelatin  with  a  pH  <  4.7  turned  dark.  This  proves  that  the 
silver  gelatinate  gave  off  its  silver  as  soon  as  pH  became  c  4.7.  The  photograph  was  taken  after  three 
weeks'  exposure  to  light.  The  lower  row  of  figures  at  the  base  of  the  figure  gives  the  pH  of  the  gelatin  solu- 
tion for  each  test  tube,  the  upi>er  row  at  the  top  of  each  test  tube  gives  the  concentration  of  acid  used  to 
bring  the  gelatin  to  the  pH  indicated.  In  one  point  the  photograph  is  misleading,  the  gelatin  solution  with 
pH  =  4.7  was  white,  but  opaque,  due  to  the  fact  that  the  gelatin  at  this  point  is  insoluble  at  room  tem- 
perature. The  gelatin  solution  with  pH  =  4.8  was  clear,  but  brown,  indicating  that  it  contained  silver. 
While  in  the  photograph  tubes  with  pH  =4.7  and  4.8  look  alike,  they  were  in  reality  strikingly  different. 


COLLOID  CHEMISTRY  AND  MEDICINE  869 

in  each  funnel,  and  then  after  having  washed  off  the  excess  of  acid 
treat  each  gram  of  gelatin  of  different  pH  with  the  same  rather  high 
concentration  (e.g.,  M/8)  of  a  salt  of  Br  or  CNS,  a  volumetric 
analysis  of  the  gelatin  after  the  removal  of  the  excess  of  the  salt 
shows  that  Br  or  CNS  exist  in  combination  with  gelatin  only 
where  pH  <  4.7. 

What  is  of  greater  significance,  however,  is  the  following  fact: 
Pauli,  (13)  Ostwald,  and  other  colloid  chemists,  have  expressed  a 
doubt  that  protein  solutions  can  show  a  true  osmotic  pressure,  and 
they  are  inclined  to  ascribe  the  "apparent**  osmotic  pressure  to  a 
"  hydra tation**  of  the  gelatin.  Since  there  are  no  measurements  for 
"hydratation**  it  is  impossible  to  put  such  speculations  to  a  scien- 
tific test.  Our  method  of  using  gelatin  in  powdered  form  and  of 
washing  away  the  excess  of  electrolyte  after  it  has  had  a  chance  to 
act  on  the  gelatin  allowed  us  to  furnish  the  molecular  data  neces- 
sary to  prove  that  the  osmotic  pressure,  swelling,  viscosity,  and 
other  physical  properties  of  gelatin  are  determined  by  the  mass  of 
gelatin  salt  formed.  Figs.  2  and  3  show  that  the  curves  for  the 
amount  of  swelling  run  approximately  parallel  to  the  curves  repre- 
senting the  amount  of  Ag  or  Br  in  combination  with  the  gelatin. 
The  same  was  found  to  be  true  for  the  curves  for  osmotic  pressure 
and  viscosity.  This  leaves  no  doubt  that  it  is  the  number  of  mole- 
cules of  gelatin  salt  formed  which  determines  the  osmotic  pressure 
— as  the  classical  theory  of  van't  Hoff  demands. 

The  influence  of  electrolytes  upon  the  physical  properties  of 
proteins  can  be  accounted  for  on  the  assumption  that  gelatin  (like 
proteins  in  general)  is  an  amphoteric  electrolyte  which  at  the  iso- 
electric point  is  practically  insoluble  while  its  salts  are  soluble; 
and  under  these  conditions  it  is  natural  that  the  osmotic  pressure 
should  increase  with  the  number  of  particles  brought  into  solution. 
Procter  (14)  has  developed  an  osmotic  theory  of  swelling  by  acid 
according  to  which  the  quantity  of  gelatin  salt  formed  under  the 
influence  of  acid  determines  the  swelHng.  This  may  explain  why  the 
curves  for  osmotic  pressure  and  swelling  of  gelatin  run  parallel. 

The  hypothesis  of  the  colloid  chemists  that  the  influence  of 
electrolytes  upon  the  swelling,  viscosity,  and  the  other  properties 
of  gelatin  is  due  to  a  hydratation  of  gelatin  ions  becomes  doubtful 
in  the  light  of  facts  recently  found  by  the  author.  Pauli  and  other 


870 


COLLOID  CHEMISTRY  AND  MEDICINE 


Fig.  2.  Gelatin  treated  with 
different  concentrations  of  HNO», 
from  M/8  to  M/8192,  washed, 
and  then  treated  with  the  same 
concentration  of  AgNOi  (M/16), 
and  then  washed  again.  Abscissae 
show  concentrations  of  acid  used. 
The  final  pH  of  the  gelatin  solu- 
tion is  found  under  the  figure  for 
the  concentration  of  acid  used. 

The  ordinates  of  the  lower 
curve  give  the  values  for  the 
silver  found  in  combination  with 
the  gelatin.  The  curve  shows  that 
at  the  isoelectric  point  (pH  =4.7) 
and  on  the  acid  side  of  the  iso- 
electric point,  the  gelatin  was 
practically  free  from  silver.  On 
the  more  alkaline  side  the  amount 
of  silver  found  in  combination 
with  the  gelatin  increased  with 
the  pH.  This  proves  that  gelatin 
can  combine  with  a  cation  only 
on  the  alkaline  side  from  the 
isoelectric  point,  and  this  is  cor- 
roborated by  the  fact  that  on  the 
alkaline  side  from  the  isoelectric 
point  only  was  the  gelatin  dark- 
ened by  light.  The  ordinates  of 
the  upper  curve  are  the  values  for 
the  swelling  of  the  same  gelatin.  On  the  alkaline  side  from  the  isoelectric  point,  where 
the  gelatin  had  combined  with  silver,  the  curve  for  swelling  runs  parallel  to  the  curve 
for  Sliver  ^elatinate  formed.  It  was,  therefore,  the  relative  mass  of  silver  gelatinate 
formed  which  determined  the  physical  properties  of  gelatin. 


90 
80 
70 
60 
50 
40 
30 
20 
10 
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JjAgNO* 


Fig.  3.  Gelatin  treated  with 
different  concentrations  of  HNOi, 
washed,  treated  with  M/8  NaBr, 
and  washed  again.  The  ordinates 
of  the  lower  curve  are  the  values 
of  Br  in  combination  with  gela- 
tin, showing  that  on  the  right 
(alkaline)  side  from  the  isoelectric 
point  and  at  the  isoelectric  point 
gelatin  contains  no  Br,  while  on 
the  left,  more  acid  side  from  the 
isoelectric  point,  the  amount  of 
the  Br  found  increases  with  the 
pH.  The  ordinates  of  the  upper 
curve  represent  the  swelling  of 
the  same  gelatin.  The  two  curves 
on  the  left  side  are  almost  par- 
allel, showing  that  the  degree  of 
swelling  is  determined  by  the 
relative  mass  of  the  gelatin  bro- 
mide (or  nitrate)  formed. 


Tfeglon  of  Gelatin  -Br 
and  Gelatin- NQ> 


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M_    M_  M_  M      C 
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pH  17    18  16  19  41    42  4A  47  il  &6  6A  66  7.0  71. 
J^Na.Br 


COLLOID  CHEMISTRY  AND  MEDICINE  871 

colloid  chemists  assume  that  when  protein  is  ionized  it  is  surrounded 
by  a  jacket  of  water  molecules,  and  the  more  protein  molecules 
are  ionized  the  greater  this  hydratation.  The  idea  that  ions  in 
watery  solution  are  surrounded  by  a  water  jacket  the  writer  is  not 
inclined  to  doubt.  He  questions,  however,  the  correctness  of  the 
view  that  this  hydratation  determines  the  swelling,  viscosity,  and 
the  osmotic  pressure  of  gelatin.  It  is  obvious  that  according  to  this 
hypothesis  the  swelling  or  osmotic  pressure  of  gelatin  should  increase 
ceteris  paribus  with  the  increase  of  ionization.  The  colloid  chemists 
who  hold  such  a  view  have  never  put  it  to  a  test  by  measuring  the 
conductivity  of  their  protein  solution,  probably  on  account  of  the 
fact  that  with  their  method  of  investigating  the  effect  of  electro- 
lytes on  colloids  in  the  presence  of  an  excess  of  electrolyte  this  was 
very  difficult.  The  writer's  method  of  removing  the  excess  of  elec- 
trolytes after  they  had  acted  on  the  colloid  permitted  the  measure- 
ments of  conductivity  necessary  to  test  the  hydratation  hypothesis, 
with  the  unexpected  result  that  the  differences  in  conductivity 
which  according  to  the  colloidal  hypotheses  should  exist  are  not 
found.  The  writer  observed  that  gelatin  salts  with  monovalent 
cation  (Li,  Na,  K,  NH4)  have  an  osmotic  pressure  about  three  times 
as  great  as  gelatin  salts  in  the  same  concentration  with  a  bivalent 
cation,  like  Ca  or  Ba.  The  swelling  and  viscosity  for  these  two 
types  of  gelatin  salts  yield  curves  similar  to  those  of  osmotic  pres- 
sure. According  to  the  colloidal  hypothesis  this  would  mean  that 
the  gelatin  salts  with  monovalent  cation  are  ionized  three  times, 
as  much  as  the  gelatin  salts  with  bivalent  cation  of  the  same  con- 
centration. Measurements  of  the  conductivity  have  shown  that 
solutions  of  Li,  Na,  Ca,  and  Ba  gelatinate  of  the  same  concentra- 
tion have  practically  identical  conductivity.  This  eliminates  the 
colloidal  hypothesis  that  osmotic  pressure  and  swelling  of  gelatin 
are  due  to  a  hydratation  of  protein  ions.  On  the  basis  of  general  chem- 
istry a  simple  explanation  for  these  facts  is  found  on  the  assumption 
that  calcium  gelatinate  forms  molecules  of  the  type  Ca2  gelatin4, 
dissociating  into  three  particles,  two  positively  charged  calcium  ions 
and  one  aggregate  of  four  gelatin  ions  with  four  negative  charges; 
while  sodium  gelatinate  dissociates  into  one  f>ositive  Na  and  one 
negative  gelatin  ion.  Eight  particles  of  the  latter  will  therefore  carry 
as  many  charges  as  three  particles  of  the  former,  which  leads  to  a 


872  COLLOID  CHEMISTRY  AND  MEDICINE 

ratio  of  osmotic  pressures  of  3  :  8  and  a  ratio  of  conductivity  of 
1:1,  which  were  actually  found.  What  is  stated  here  for  sodium  and 
calcium  gelatinate  holds  also  for  gelatin  chloride  and  gelatin  sul- 
phate, their  conductivities  being  alike,  while  their  curves  of  swelling, 
osmotic  pressure,  and  viscosity  differ  in  a  way  similar  to  that  between 
Na  and  Ca  gelatinate.  The  hydratation  hypothesis  of  swelling  and 
osmotic  pressure  of  colloids  is  therefore  no  longer  tenable. 

We  thus  see  that  the  assumption  of  the  non-validity  of  the  laws 
of  general  chemistry  for  proteins  (and  other  colloids)  is  not  supported 
by  fact.  The  error  was  due  to  the  shortcomings  of  the  methods  used 
by  colloid  chemists  in  this  work,  two  of  which  have  been  mentioned, 
namely,  first  the  non-consideration  of  the  hydrogen  ion  concentration 
of  their  solutions,  and,  second,  the  investigation  of  the  proteins  in 
the  presence  of  an  excess  of  electrolytes.  The  avoidance  of  these 
two  sources  of  error  has  not  only  shown  the  validity  of  the  laws  of 
general  chemistry  for  proteins  but  has  also  led  to  a  simplification  of 
protein  chemistry. 

BIBLIOGRAPHY 

1.  Arrhenius,  S.,  "Immunochemistry,"  New  York,  1907. 

2.  Langmuir,  I.,  J,  Am.  Cbem.  Soc,  1918,  XL,  1361. 

3.  Oswald,  Wo.,  "Die  allgemeinen  Kennzeichen  der  organisierten  Sub- 

stanz;"  P.  Hinneberg,  "Die  Kultur  der  Gegenwart,  Allgemeine  Bio- 
logie,"  Leipzig,  1915,  p.  167. 

4.  Fischer,  M.  H.,  J.  Am.  M.  Ass.^  1913,  LX,  348. 

5.  Nasse,  O.,  Arcb.  J.  d.  ges.  Physiol,  1869,  II,  97;  Loeb,  J.,  Arch.  J.  d. 

ges.  PbysioL,  1897-98,  LXIX,  i. 

6.  Overton,  E.,  Arcb.f.  d.  ges.  Pb/siol,  1902,  XCII,  115. 

7.  Hober,  R.,  Biol.  CentralbL,  191 1,  XXXI,  575. 

8.  Loeb,  J.,  Science,  1913,  XXXVII,  430. 

9.  Hofmeister,  F.,  Arcb.f.  exper.  Patb.  u.  PbarmakoL,  1891,  XXVIII,  210. 

10.  Lillie,  R.  S.,  Am.  J.  PbysioL,  1907-8,  XX,  127. 

11.  Loeb,  J.,  J.  Gen.  PbysioL,  1918-19,  I,  39,  237,  363,  483,  559. 

12.  Michaelis,  L.,  "Die  Wasserstoflfionenkonzentration,"  Berlin,  1914. 

13.  Pauli,  W.,  Fortscbr.  naturwiss.  Forscbung,  1912,  IV,  245. 

14.  Procter,  H.  R.,  and  Wilson,  J.  A.,  J.  Cbem.  Soc,  1916,  CIX,  307; 

Procter  and  Burton,  D.,  J.  Soc.  Cbem.  Indust.,  191 6,  XXXV. 


A  FEW  THOUGHTS  ON  THE  VIS  MEDICATRIX 

NATUR.€ 

By  Robert  Dawson  Rudolf,  C.B.E.,  M.D.  (Edin.),  F.R.C.P. 

Colonel,  C.A.M.C.,  Consulting  Physician  to  the  Canadian  Forces  in  England. 
Professor  of  Therapeutics  in  the  University  of  Toronto 

THE  fact  that  disease  often  tends  to  disappear,  even  when  not 
treated,  has  only  been  a  recent  realisation  in  the  history  of 
medicine.  It  is,  nevertheless,  true  that  the  Father  of  Medicine 
knew  of  it,  as  shown  by  his  teachings  that  disease  was,  equally  with 
life,  a  process  governed  by  natural  laws  which  indicated  the  spon- 
taneous and  normal  direction  of  recovery,  and  by  following  which 
alone  could  the  physician  succeed. 

"The  healing  power  of  nature  was  a  Hippocratic  doctrine.  Not  that 
Hippocrates  taught,  as  he  was  afterwards  reproached  with  teaching,  that 
nature  is  sufficient  for  the  cure  of  disease,  for  he  held  strongly  the  efficacy 
of  art.  But  he  recognised,  at  least  in  acute  diseases,  a  natural  process  which 
the  humours  went  through, — being  first  of  all  crude,  then  passing  through 
coction  or  digestion,  and  finally  being  expelled  by  resolution  or  crisis 
through  one  of  the  natural  channels  of  the  body.  The  duty  of  the  physician 
was  to  foresee  these  changes  and  to  assist  or  not  to  hinder  them;  so  that 
the  sick  man  might  conquer  the  disease,  with  the  help  of  the  physician." 
(Encycloped.  Britann.,  XV.,  800.) 

Alas  1  that  the  profession  in  the  succeeding  centuries  should  have 
fallen  so  far  from  this  simple  doctrine. 

From  the  earliest  times  until  now,  the  theories  of  the  origin  and 
nature  of  diseases  have  varied  greatly — at  one  time  these  were  due 
to  evil  spirits;  at  another  to  various  humours;  at  yet  another  to  the 
influence  of  the  heavenly  bodies,  and  so  on;  but,  while  treatment 
always  varied  according  to  the  prevaiHng  theory,  some  treatment 
there  always  was,  and  when  the  patient  recovered  he  was  considered 
to  have  been  cured  by  the  treatment,  and  when  he  died  then  he  did  so 
in  spite  of  it. 

873 


874       THOUGHTS  ON  VIS  MEDICATRIX  NATUR.€ 

But,  fortunately  for  medicine,  some  hundred  and  fifty  years 
ago  Hahnemann  appeared.  He  condemned  in  no  mild  terms  the 
heroic  treatment  of  his  day. 

"The  old  school  of  medicine  [sic],  [he  wrote]  presupposes  the 
existence  sometimes  of  excess  of  blood  (plethora — which  is  never  present), 
sometimes  of  morbid  matters  and  acridities,  hence  it  taps  off  the  life's 
blood  and  exerts  itself  either  to  clear  away  the  imaginary  morbid  matter, 
or  conducts  it  elsewhere  (by  emetics,  purgatives,  sialagogues,  diaphoretics, 
diuretics,  drawing  plasters,  setons,  issues,  etc.),  in  the  vain  belief  that  the 
disease  will  thereby  be  weakened  and  substantially  eradicated;  in  face 
of  which  the  patient's  sufferings  are  thereby  increased,  and  by  such  rather 
painful  appliances  the  forces  and  nutritive  juices,  indispensable  to  the 
curative  process,  are  abstracted  from  the  organism.  It  assails  the  body 
with  large  doses  of  powerful  medicines,  often  repeated  in  rapid  succession 
for  a  long  time,  whose  long-enduring  and  often  frightful  effects  it  knows 
not,  and  which  it,  purposely  it  would  almost  seem,  makes  unrecognisable 
by  the  co-mingling  of  several  such  unknown  substances  in  one  prescrip- 
tion, and  by  their  long-continued  employment  it  develops  in  the  body  new 
and  often  ineradicable  medicinal  diseases."  (Hahnemann,  "Organon  of 
Medicine,  vii.) 

And  a  little  later  he  writes: 

"It  is  under  the  old  physician  who  has  been  at  last  gradually  con- 
vinced of  the  mischievous  nature  of  the  so-called  art,  after  many  years 
of  misdeeds,  and  who  only  continues  to  treat  the  severest  diseases  with 
strawberry  syrup  mixed  with  plantain  water  (i.e.,  nothing)  that  the 
smallest  number  are  injured  and  die." 

If  only  Hahnemann  had  stopped  here,  what  a  new  era  he  would 
have  initiated  I  but,  instead,  he  went  on  to  propound  a  very  fantastic 
theory  of  disease,  so  that  he  only  endeavoured  to  replace  the  current 
theories  (of  plethora,  morbid  matters,  and  acridities)  by  another, 
equally  unfounded  in  pathology.  He  passionately  rejected,  indeed, 
pathology  and  morbid  anatomy,  and  believed  only  in  "the  derange- 
ments of  the  spiritual  power  that  animates  the  human  body."  As 
regards  treatment,  he  pressed  his  theory  of  similia  similibus  curantur 
(which  had,  indeed,  been  outlined  by  Haller,  and  by  Tommasini,  an 
Italian  "contra-stimulist").  "He  ascribed  the  effects  of  drugs  to  the 
spiritual  power  which  lies  hid  in  the  inner  nature  of  medicines,"  and, 
further,  advocated  the  principle  that  the  smaller  the  dose  of  these 


THOUGHTS  ON  VIS  MEDICATRIX  NATURE      875 

medicines,  the  greater  their  power.  Hahnemann  was  much  persecuted 
on  account  of  his  views,  but,  nevertheless,  had  a  great  following, 
and  by  the  introduction  of  these  microscopic  doses,  he  (all  unwit- 
tingly) elaborated  upon  a  large  scale  the  experiment  of  seeing  what 
happened  in  disease  when  it  was  uninterfered  with  by  medicines. 
His  results  must  have  been  much  better  than  those  of  the  "heroic** 
School, — better,  indeed,  than  if  he  had  given  no  medicine  at  all, 
for  by  the  administration  of  his  inert  fractional  doses,  he  would 
meet  the  craving  of  his  patients  for  some  treatment,  and  thus 
enlisted  on  his  side  the  all-powerful  influences  of  hope  and  faith. 
I  say  that  he  performed  this  great  experiment  into  the  power  of 
nature  to  cure  "unwittingly,"  for, 

"It  was  a  very  essential  part  of  his  teaching  that  nature  is  a  bad  phy- 
sician and  not  to  be  much  trusted;  that  drugs  are  the  real  curative  agents, 
provided  by  the  beneficence  of  the  Almighty."  (Encyclop.  Brit.,  XII,  128.) 

Hahnemann*s  treatment  was  at  least  not  actively  harmful,  and 
as  he  lived  at  the  time  when,  as  already  said,  the  practice  of  giving 
enormous  doses  was  all-prevalent,  when  the  "stimulus"  theory  of 
John  Brown  and  the  "contra-stimulus**  method  of  Rasori  (copious 
bleeding  and  depressing  remedies,  such  as  antimony)  held  sway, 
it  is  small  wonder  that  he  had  many  followers.  But,  in  spite  of  his 
work  and  writings,  "heroic"  therapy  continued,  and  we  have  Joseph 
Bigelow  writing  sadly  in  i860  (in  his  "Rational  Medicine"): 

"  I  sincerely  believe  that  the  unbiassed  opinion  of  most  medical  men 
of  some  judgment  and  long  experience  is  made  up,  that  the  amount  of 
death  and  disaster  in  the  world  would  be  less,  if  all  disease  were  left  to 
itself,  than  it  now  is  under  the  multiform,  reckless  and  contradictory  modes 
of  practice,  good  and  bad,  with  which  practitioners  of  adverse  denomina- 
tions, carry  on  their  differences  at  the  exp)ense  of  their  patients." 

As  R.  C.  Ewing  wrote  in  1896  {Med.  Rec,  June  13,  1896,  845), 

"  It  was  not  until  a  much  later  p)eriod  that  physicians  recognised  that 
there  is  a  something,  and  they  know  not  what  it  is,  aside  from  drugs, 
which  plays  an  important  r6Ie  in  the  eradication  of  disease;  and  the 
highest  minds  of  the  present  day  are  earnestly  seeking  a  solution  of  the 
mystery.  Have  they  found  it,  and  can  it  be  explained  by  the  'exhaustion* 
theory  of  Pasteur;  the  'excretory*  theory  of  Chauveau;  the  'ozonised* 
theory  of  Traube;  the  'tolerance  of  poisons'  theory  of  Sternberg;  the 


876      THOUGHTS  ON  VIS  MEDICATRIX  NATURE 

'phagocytic'  theory  of  MetchnikofF,  or  the  'immunising'  theory  of 
Vaughan?  I  shall  let  them  answer, " 

and  although  we  can  add  several  more  theories  since  then,  who  can 
deny  that  the  essential  nature  of  immunity  still  remains  to  be  settled? 

But,  as  regards  the  question  of  treatment,  we  can  at  least  now 
pride  ourselves  on  the  general  recognition  that  there  exist  certain 
natural  forces  which  tend  to  eradicate  disease,  apart  from  any 
medical  treatment.  Evidence  of  the  natural  tendency  to  recovery  is 
everywhere  seen  in  the  vegetable  and  animal  kingdoms.  Generally 
speaking,  the  lower  the  organism  in  the  scale  of  evolution,  the 
greater  and  more  complete  is  the  tendency  to  restoration.  A  small 
twig,  separated  from  the  parent  stem,  will,  when  planted,  grow 
into  a  new  tree.  If  a  hydra  be  cut  in  two,  its  basal  end  will  grow  a 
new  mouth,  and  its  oral  end  another  pedicle.  One  limb  of  a  star- 
fish can  sometimes  reform  the  whole  animal.  Going  a  little  higher 
in  the  scale,  a  lizard,  when  it  loses  its  tail,  simply  grows  a  new  one, 
but  the  severed  tail  dies.  A  frog  or  a  lobster  similarly  has  a  lost  limb 
or  claw  restored.  In  mammals  the  reparative  process  is  not  so 
complete,  but  if  a  portion  of  the  liver  of  a  cat  or  dog  be  removed,  it 
will  be  largely  and  quickly  restored.  Such  are  a  few  examples  of 
nature's  power  of  restoring  tissues. 

As  regards  function,  the  body  has  similarly  great  powers  of  adap- 
tation to  disturbance,  as  seen  when  one  kidney  will  take  on  the  function 
of  both,  and  when  in  severe  anaemia  the  yellow  marrow  of  the  long 
bones  becomes  red  with  its  activity  in  producing  red  blood  corpuscles. 

The  healing  of  an  aseptic  wound  shews  the  natural  forces  all 
intent  upon  the  restoration  of  the  part.  But  when  infection  has 
occurred,  then  it  is  seen  that  the  natural  forces  are  not  all  upon  the 
side  of  the  suflferer.  The  tissues  and  body  fluids  are  provided  with 
certain  powers  of  fighting  the  bacterial  invaders,  but  the  invaders 
are  also  provided  by  neutral  nature  with  powers  that  help  them. 
There  are,  from  the  patient's  viewpoint,  both  good  and  bad  forces  of 
nature;  it  is  only  the  former  that  constitute  the  vis  medicatrix  naturae. 

We  may  view  Nature  as  the  personification  of  the  natural  forces, 
and  realise  that  she  is  neutral  and  would  as  lief  that  the  man  die 
as  that  he  survive  the  infection.  When  a  cancer  becomes  emplanted 
in  the  tissues,  nature  encourages  its  growth,  and  nothing  but  the 


THOUGHTS  ON  VIS  MEDICATRIX  NATURAE      877 

surgeon's  interference  will  save  the  patient.  In  the  same  way,  it  is 
in  accordance  with  nature's  laws  that  a  tapeworm  flourishes  in  the 
intestine  or  the  acarus  scabei  infects  the  skin.  Both  will  continue 
indefinitely  unless  they  are  treated  medicinally.  Hence,  while 
the  physician  must  allow  all  natural  forces  that  tend  to  help  his 
patient  to  have  full  sway,  it  is  often  necessary  for  him  to  interfere 
with  the  course  of  nature,  and  here  we  see  the  limitations  of  purely 
"expectant"  treatment. 

Nature  may  be  compared  to  an  absolutely  unbiassed  judge,  who 
dispenses  the  laws  and  exacts  the  penalties.  And  the  laws  are  not 
human  laws,  but  natural  ones.  A  man  poisons  himself  with  alcohol, 
and  the  Court  decides  that  he  shall  suff"er  and  perhaps  die.  Another 
man  shuts  himself  up  in  a  bad  atmosphere,  and  there,  burning  the 
midnight  oil,  wears  himself  out  working,  perhaps  in  order  that  his 
loved  ones  may  live.  But  the  verdict  is  that  the  tubercle  baciUi, 
which,  following  natural  laws,  have  emplanted  themselves  in  his 
depressed  tissues,  shall  win.  The  Court  of  nature  is  indeed  one  where 
natural  laws  are  inexorably  administered,  but  where  sympathy  and 
pity  are  unknown. 

But  the  practitioner  is  not  unbiassed,  but  wholly  on  the  side  of 
his  patient.  It  is  not  an  indiff"erent  thing  to  him  whether  the  cancer 
or  the  man  win;  whether  the  tubercle  or  the  patient  flourish.  The 
alcoholic  may  have  broken  both  natural  and  moral  laws,  but  he 
must  be  saved,  if  possible,  in  spite  of  his  natural  and  moral  sins. 

How,  then,  can  the  medical  man  best  help  his  patient  in  his 
struggle  back  to  health?  In  the  first  place,  he  must  himself  know 
the  natural  laws — the  natural  history  of  disease — just  as  a  lawyer, 
in  order  to  help  his  client,  must  know  the  laws  of  the  country. 
Then  he  must  needs  instruct  his  patient  (or  better  still  the  man  be- 
fore he  becomes  ill)  as  to  the  consequences  of  breaking  the  natural 
laws.  Although  all  men  must  eventually  die,  how  much  life  and  needless 
sufi'ering  could  be  saved  by  the  instruction  of  the  public  in  the  sim- 
plest laws  of  health — the  prevention  of  disease  rather  than  its 
treatment! 

When  a  man  becomes  ill,  his  physician  will  place  him  in  such 
surroundings  that  all  the  natural  forces  in  his  favour  will  have  full 
scope.  Rest,  fresh  air,  and  sunshine  and  nourishing  food  all  help 
to  raise  the  patient's  resistance  to  infection  and  are  opposed  to  the 


878      THOUGHTS  ON  VIS  MEDICATRIX  NATUR.^ 

infecting  agents.  Very  often  the  medical  man  can  increase  the 
natural  endeavours  and  thus  help  nature  in  the  cure.  A  man  breaks 
his  leg,  and  nature  will  rest  the  limb  by  causing  pain  on  movement. 
But  the  surgeon  goes  further,  and  by  the  application  of  splints 
increases  the  immobility  and  thus  hastens  the  knitting  of  the  bones. 
An  individual  swallows  an  irritant  p)oison  and  nature  causes  him  to 
vomit,  but  his  cure  will  be  hastened  and  made  more  complete  by 
the  timely  use  of  an  emetic  or  gastric  lavage.  Often  the  medical  man 
must  go  still  further.  The  cancer  must  be  eradicated  by  the  knife 
or  it  will  inevitably  grow  until  it  causes  death.  An  impacted  gall  stone 
or  ureteral  calculus  may  have  to  be  removed,  and  so  on.  Tapeworms 
and  many  other  parasites  will  persist  unless  they  are  removed  by 
therapeutic  means. 

In  other  cases,  for  example  in  infections,  the  body  tissues  may 
win  in  the  fight,  unaided,  but  the  physician  can  do  much  to  sway  the 
struggle  in  the  right  direction.  Vaccines,  by  increasing  active 
immunity,  and  antitoxins,  by  producing  passive  immunity,  are 
examples  here.  In  a  few  instances  drugs  will  directly  assist  in  the 
struggle,  as  in  the  case  of  mercury  and  arsenic  in  syphilis  and 
quinine  in  malaria.  But  while  some  diseases  can  thus  be  treated 
specifically,  the  great  majority  of  human  ailments  are  yet  beyond 
such  satisfactory  attack. 

But  the  medical  man*s  duty,  and  privilege,  is  not  only  to  "cure** 
disease  (or  rather  diseased  persons),  but  also  to  relieve  suffering. 
And  it  should,  further,  always  be  remembered  that  in  relieving  suf- 
fering, by  giving  the  patient  rest  and  ease,  conserving  his  strength, 
we  are  doing  more  than  this,  we  are  helping  the  natural  tendencies 
to  cure — we  are  giving  these  forces  time  and  opportunity  to  act. 
Who  has  not  seen  the  whole  aspect  of  a  pneumonia  patient  changed 
for  the  better  by  a  timely  dose  of  morphia?  The  man  has  perhaps 
not  slept  for  days  and  is  nearly  worn  out,  and  his  resistance  almost 
gone,  and  then,  following  the  opiate,  he  gets  some  hours  of  sleep  and 
rest  and  thus  is  strong  enough  to  reach  his  crisis.  Nature  has  in 
time  conferred  upon  him  immunity,  but  he  might  not  have  reached 
this  goal  if  he  had  not  slept. 

I  remember  many  years  ago  seeing  the  good  effects  of  a  narcotic 
in  the  case  of  a  pet  dog.  The  animal  had  suffered  so  much  from  an 
irritating  skin  condition  that  it  was  reduced  to  skin  and  bone.  In 


THOUGHTS  ON  VIS  MEDICATRIX  NATUR.€      879 

family  conclave  it  was  decided  to  put  it  out  of  its  suffering,  and 
a  huge  dose  of  opium  was  given,  and  the  poor  beast  was  shut  up  in 
a  coal  cellar  to  die.  Next  morning  he  was  found  not  to  be  dead,  but 
to  be  sleeping  heavily,  and  this  went  on  for  many  hours.  Then  he 
awoke,  peaceful  and  hungry,  ate  heartily,  and  in  a  week  or  two  was 
well.  The  profound  sleep  gave  him  ease  and  nature  did  the  rest. 

One  might  enumerate  many  wearing  symptoms,  such  as  per- 
sistent insomnia,  high  fever,  a  trigeminal  neuralgia,  severe  con- 
stipation or  diarrhea,  in  which  purely  symptomatic  treatment, 
where  nothing  more  is  found  to  be  possible  (or  in  addition  to  more 
radical  therapy)  may  not  only  relieve  suffering,  but  may  go  far 
towards  helping  nature  to  cure. 

Symptomatic  treatment  is  sometimes  scoffed  at  (and  rightly  so, 
when  anything  more  radical  can  be  done),  but  very  often  it  is  all 
that  is  within  our  powers,  and  he  is  a  bad  physician,  indeed,  who 
does  not  then  employ  it.  Even  in  mortal  disease,  such  as  inoperable 
cancer,  surcease  from  pain  and  distress  will  often  not  only  relieve 
the  sufferer  for  the  time  being,  but  will  actually  prolong  hfe  for 
weeks  or  even  months.  In  symptomatic  therapy  drugs  are  chiefly 
used;  hydropathy  is  often  of  value  here,  but,  after  all,  water  is  a 
pharmacopoeial  drug. 

It  has  been  well  said  that  drugs  sometimes  cure,  often  relieve, 
and  always  console.  We  must  remember  that  one  of  the  most  power- 
ful influences  towards  a  return  to  health  is  Hope.  "What  doctor," 
plaintively  asks  that  delightful  but  highly-strung  French  writer, 
Amiel,  "possesses  such  curative  resources  as  are  latent  in  a  spark  of 
happiness  or  a  single  ray  of  hope?"  But  it  is  surely  one  of  the  highest 
duties  of  the  doctor  to  endeavour  to  inspire  this  hope,  up>on  which 
so  much  of  his  success  depends,  not  only  in  so-called  "functional" 
conditions,  but  in  organic  disease  itself. 

He  is  a  gruesome  physician  who  tells  his  patient  that  no  treat- 
ment will  do  him  any  good.  In  the  first  place  it  is  not  true.  By  this, 
it  is  not  meant  that  we  should  always  give  medicines.  Medical  treat- 
ment is  not  necessarily  medicinal,  but  includes  every  kind  of  phys- 
ical, psychic,  and  other  form  of  therapy. 

As  an  old  friend  of  mine  expressed  it:  "There  is  more  in  Medicine 
than  medicine  I" 


SOURCES  OF  INTELLECTUAL  POWER 
By  William  Browning,  Ph.B.,  M.D., 

Professor  of  Neurology,  Long  Island  Medical  College;  President  of  the  Association  of 

Medical  Librarians 

QUESTIONS  of  the  character  suggested  by  the  superscrip- 
tion inevitably  come  up  when  we  consider  the  personality 
of  our  leaders.  It  is  a  problem  of  the  highest  human 
■'interest.  Suggestions  of  it  lurk  in  many  discussions,  and 
are  embodied  in  most  systems  of  education.  Yet  not  often  is  there 
an  attempt  at  direct  answers.  The  subject  can  the  more  suitably 
be  presented  here,  as  the  material  on  which  it  is  based,  though  of 
general  import,  is  largely  of  medical  derivation. 

There  are  of  course  many  such  sources.  To  say  that  they  are 
covered  by  the  biologist's  formula  of  Heredity  and  Environment 
does  not  advance  things  materially.  Whenever  there  is  a  rush  of 
newer  methods  there  is  strong  likelihood  that  older  ones  will  be 
neglected  if  not  prematurely  discarded.  And  so  often  in  medicine 
we  see  new  achievements  presently  paralleled  by  improvements 
along  former  lines;  in  fortunate  cases,  then,  each  finds  its  own  se- 
lective field  or  happily  serves  to  complement  the  other.  Something 
of  this  kind  may  hold  for  recent  developments  in  psychology  and 
genetics,  and  here  certainly  no  aids,  new  or  old,  should  be  cast 
aside. 

The  proof  of  intellectual  power  is  sought  naturally  at  the  top, 
not  the  bottom  of  the  scale.  As  to  what  constitutes  or  is  evidence 
of  superior  intellectual  power  opinions  may  differ.  In  the  sense  here 
intended  it  represents  the  highest  expression  of  human  thought  and 
activity.  There  are  many  grades  and  nuances.  Mere  executive  ability 
and  acquisitiveness,  for  example,  however  useful  qualities,  are  at 
times  exhibited  by  animals  in  notable  degree;  and  cannot  con- 
sequently just  of  themselves  be  regarded  as  marks  of  high  intel- 
lectuality. It  is  the  later  or  superposed  acquirements,  racial  and 

880 


SOURCES  OF  INTELLECTUAL  POWER  88 1 

personal,  that  can  fafrly  be  accounted  the  higher.  Hence  only  the 
later  or  proximate  Sources  are  here  of  concern,  a  selection  of  two  of 
which  will  be  briefly  considered. 

L  Medical  Heredity  as  a  Genetic  Asset.  A  plan  for  esti- 
mating Sources  that  does  not  appear  to  have  been  applied  may  be 
called  the  Group  or  Epochal  method.  This  permits  a  more  exact 
determination  in  particular  instances,  and  is  in  so  far  a  scientific 
line  of  approach. 

In  this  country,  especially,  great  storehouses  of  possible  material 
for  study,  collected  for  other  purposes,  it  is  true,  are  at  hand  in  our 
libraries.  It  is  the  more  in  order  to  call  attention  to  this,  as  the  one 
we  wish  to  honor  has  been  such  a  valued  supporter  of  our  library 
system.  This  is  a  natural-experimental  plan.  So  far  as  concerns  the 
human  side,  that  of  chief  and  final  importance  to  us,  nature — in 
the  guise  of  matings  and  progeny — is  continually  making  experi- 
ments wholesale  for  us,  if  we  but  seek  them  out,  and  such  as  can 
never  be  equaled  by  those  on  animals.  Our  library  files  carry  the 
protocols. 

Two  groups  of  epochal  leaders  with  a  common  index  will  suffice 
for  illustration. 

(a).  American  neurology,  aside  from  psychiatry,  developed  from 
the  time  of  the  Civil  War.  Half  a  dozen  names  will  be  recognized  by 
those  familiar  with  the  facts,  as  embracing  the  main  contingent  of 
original  contributors  to  that  foundation.  These  were  not  only  great 
as  original  workers,  but  they  started  a  new  discipline  here,  did  a 
pioneer  work,  and,  so  far  as  concerns  this  country,  created  an  epoch 
in  their  specialty,  one  of  the  most  concrete  developments  in  our 
medical  history.  The  branch  thus  established  can,  moreover,  claim 
a  leading  place  on  the  intellectual  side  of  medical  work.  If  in  such  a 
group  a  common  index  can  be  made  out,  it  must  rank  as  a  distinct 
and  creative  intellectual  force.  Such  an  index  can  be  discerned  by 
inspection  of  their  line  of  descent. 

There  were  others  who  did  invaluable  work,  but  these  are  the 
men  whose  contributions  stand  out. 

I.  S.  Weir  Mitchell,  1829-1914,  first  authority  on  nerve  injuries,  origi- 
nator of  the  rest  cure,  b.  Phila.,  son  of  John  K.  Mitchell,  M.D.  (i  798-1 858), 
grands,  of  Dr.  Alexander  Mitchell  (1768- 1804),  and  g.  g.  s.  of  a  Scotch 
physician. 


882  SOURCES  OF  INTELLECTUAL  POWER 

2.  Edouard  Seguin,  1812-80,  authority  on  sub-mentals,  and  institutor 
of  our  first  school  for  them,  b.  France,  s.  of  Dr.  T.  O.  Seguin,  and  g.  s.  of  a 
physician. 

3.  Edward  C.  Seguin,  1843-98,  first  professor  of  neurology  at  P.  &  S., 
editor,  well  known  for  his  contributions,  b.  France,  s.  of  preceding, 

4.  Wm.  A.  Hammond,  1 828-1 900,  author  of  first  and  long  standard 
American  work  on  neurology,  original  describer  of  athetosis,  s.  of  Dr. 
John  W.  Hammond  of  Md. 

5.  Geo.  M.  Beard,  1839-83,  an  original  describer  of  neurasthenia  and 
general  electrization,  b.  Conn.,  g.  s.  of  Dr.  Daniel  Beard  (1767-1815), 
g.  g.  s.  of  Dr.  Spencer  Field  (1754-1801),  and  g.g.g.s.  of  Dr.  John  Frink 
(1731-1807).  Beard's  last  call  for  "more  light"  may  have  come  from 
theological  inheritance. 

6.  John  C.  Dalton,  1825-89,  author  of  the  3-voI.  "Topographical 
Anatomy  of  the  Brain,"  still  the  finest  American  work  thereon,  also 
"Physiologyof  the  Cerebellum,"  b.  Mass.,  s.  of  John  C.  Dalton,  A.M.,  M.D. 
(1795-1863). 

7.  George  Huntington,  1850-1916;  his  classic  on  the  form  of  chorea 
known  by  his  name  was  published  in  1872;  b.  Long  Island,  s.  of  Geo.  L. 
Huntington,  M.D.  (1811-81),  and  g.s.  of  Dr.  Abel  Huntington  (1777-1858). 

Reviewing  this  list  it  appears  that  six  of  the  seven  were  sons  of 
physicians  while  the  seventh  was  descended  from  a  line  of  physicians. 
Five  were  grandsons  of  physicians,  and  three  were  of  even  longer 
medical  descent.  It  is  clear  that  medical  heredity  was  a  strong 
feature  of  the  group.  Hence  in  addition  to  their  own  medical  training 
we  can  look  to  their  heredity  in  the  same  line,  as  the  specific  source 
of  the  intellectual  force  that  produced  an  epochal  result.  Practically 
this  holds  whether  effected  through  internal  or  external  agencies. 
In  fact,  the  analysis  can  be  made  more  exact  and  incisive.  The 
character  of  work  undertaken  by  these  men  was,  in  accordance  with 
their  individual  training,  naturally  directed  to  something  in  the 
medical  field.  But  the  quality  of  what  they  accomplished  cannot 
be  thus  explained,  as  there  were  all  about  them  plenty  of  others  of 
medical  training  and  some  even  interested  in  the  same  special  sub- 
ject, who  failed  to  leave  any  comparable  impress.  Hence  we  must 
look  further  than  to  their  personal  calling  for  the  source  of  their 
power,  for  a  psychic  gene  which  these  men  possessed  in  common 
and  which  was  not  possessed  by  the  general  run  of  their  colleagues. 
This  is  supplied  by  the  index  of  medical  heredity. 


SOURCES  OF  INTELLECTUAL  POWER  883 

(6).  In  an  entirely  different  field  of  intense  activity  the  writer 
found  evidence  of  identical  import.  This  was  detailed  in  an  article 
on  "The  Role  of  Physicians'  Sons  in  the  Lincoln  Administration" 
(Med.Rec.f  N.  Y.,  1916,  October  28).  There  also  seven  men,  nearest 
personally  and  officially  to  Lincoln  in  the  work  of  his  administration, 
who  were  all  sons  ofmenofmedical  rearing.  They  consequently  present 
an  index  identical  with  that  for  the  Neurologic  group.  These  were 
Judge  David  Davis,  John  Hay,  Hannibal  HamHn,  Solomon  Fool 
(Senate  leader),  William  H.  Seward,  Edwin  M.  Stanton,  and  Schuy- 
ler Colfax,  "next  to  Lincoln  himself,  the  leaders  in  the  executive 
and  even  the  legislative  work  of  the  U.  S.  Government  during  that 
period." 

These  two  groups,  then,  of  quite  unrelated  character  but  with 
a  common  hereditary  index,  suffice  to  demonstrate  "the  superior 
intellectual  value  of  medical  training  and  heredity."  Questions  of 
selection  of  stock  or  of  what  other  professions  show  do  not  affect 
the  conclusion.  Medical  training  can  stand  by  itself  as  one  of  the 
highest  sources  of  intellectual  power  in  the  offspring. 

II.  Varied  Training  as  a  Mental  Activator.  The  general 
public  has  long  been  aware  of  this  principle,  and  freely  put  it  in 
practice  in  popular  forms  of  instruction  for  after-life.  Illustrations 
are  so  numerous  and  the  evidence  so  generally  accepted  that  proofs 
are  unnecessary.  The  utilization,  however,  of  this  principle,  its  appli- 
cation in  systematic  development,  falls  far  short  of  its  possibilities: 

The  old  adage,  "A  rolling  stone  gathers  no  moss,"  may  hold  in 
material  and  financial  affairs,  but  the  reverse  is  largely  true  as 
regards  intellectual  development. 

It  may  be  permissible  here  to  take  the  course  of  our  dedicatee 
for  a  text,  as  this  gave  him  varied  training  and  in  sequence  put  him 
in  touch  with  coming  men  in  every  leading  country  of  the  time. 
This  source  will  also  be  shown  by  two  illustrative  types. 

(a).  Double  Professional  Training.  This  is  a  sporadic  occurrence. 
Few  students  comparatively  can  afford  the  time  and  expense  to 
take  a  second  training,  even  in  part;  so  that  practically  it  is  a  self- 
hmiting  method.  It  is  reviewed  here,  not  as  a  plan  for  further  ex- 
ploitation (though  that  might  be  defensible),  but  as  an  illustration 
for  this  country  how  well  one  typ)e  of  varied,  training  works  out  in 
practice. 


884  SOURCES  OF  INTELLECTUAL  POWER 

There  is  an  old  and  wide  prejudice  against  change  of  calling. 
And  individuals  who  have  enjoyed  such  opportunities  are  often 
difficult  to  trace  after  gaining  distinction  in  the  second  line.  Though 
apparently  a  cumbrous  and  inadequate  plan,  as  about  the  only 
variation  available  with  us  in  the  past,  its  successes  are  the  more  in 
evidence.  Illustrations  in  plenty  might  be  adduced,  a  few  types 
must  suffice. 

1.  Mark  Hopkins,  M.D.,  S.T.D.,  1802-87,  president  of  Williams  Coll. 
(1836-72). 

2.  Theodore  D.  Woolsey,  D.D.,  LL,D.,  1801-89,  studied  law  and 
theology,  president  of  Yale  (1846-71). 

3.  William  Harris,  S.T.D.,  1 765-1829,  studied  theology  and  then 
medicine,  president  of  Columbia  Coll.  (181 1-29). 

4.  John  M.  Gregory,  LL.D.,  1822-98,  studied  law  and  theology, 
Mich,  supt.  education,  president  Kalamazoo  Coll.  and  of  Univ.  III. 

5.  Roswell  Park,  D.D.,  1807-69,  West  Pt.  183 1,  P.  E.  clergyman, 
prof,  science  Univ.  Pa.,  president  Racine  Coll. 

6.  E.  D.  Warfield,  D.D.,  1861-,  lawyer,  clergyman,  president  Miami 
Univ.  and  Lafayette  and  Wilson  Colls. 

7.  Newton  D.  Baker,  M.D.,  1871-,  lawyer,  U.  S.  Secretary  of  War. 

8.  Leonard  Wood,  M.D.,  LL.D.,  i860-,  Maj.  Gen.  and  Chief  of  Staff, 
U.  S.  A. 

9.  James  Wilkinson,  M.D.,  1 757-1 825,  General-in-Chief,  U.  S.  A. 

10.  William  H.  Harrison,  1773-1841,  student  of  medicine,  then  gained 
military  training,  President  of  U.  S. 

11.  Winfield  Scott,  1 786-1 866,  lawyer,  Gen.-in-Chief,  U.  S.  A. 

12.  Phil.  Kearny,  1815-62,  studied  law,  then  a  military  course,  Maj. 
Gen.  U.  S.  A. 

13.  James  A.  Garfield,  1831-81,  prof.  languages  and  president  Hiram 
Coll.,  lawyer,  Maj.  Gen.  U.  S.  A.,  President  U.  S. 

14.  Montgomery  Blair,  1813-83,  West  Pt.  1835,  lawyer,  U.  S.  Post- 
master General  (1861-64). 

15.  Richard  Grant  White,  1822-85,  studied  medicine,  law,  etc.,  author 
and  critic. 

16.  Luther  Jewett,  A.B.,  M.D.,  1 772-1 860,  Congregational  clergyman, 
editor,  M.C.  (Vt.  18 15-17). 

17.  Lyman  Abbott,  D.D.,  LL.D.,  1835-,  lawyer.  Congregational  clergy- 
man, editor  of  Christian  Union  and  The  Outlook. 

18.  Saml.  F.  Miller,  M.D.,  1816-90,  lawyer,  justice  U.  S.  Supreme  Ct., 
member  1877  U.  S.  Electoral  Commission. 


SOURCES  OF  INTELLECTUAL  POWER  885 

19.  Thomas  B.  Butler,  M.D.,  1806-73,  lawyer,  chief  justice  Conn. 

20.  Paul  Mumford,  1734-1805,  physician,  lawyer,  chief  justice  R.  L 

21.  Jesse  Root,  LL.D.,  1 736-1822,  clergyman,  lawyer,  chief  justice 
Conn. 

22.  William  Pinkney,  LL.D.,  1764-1822,  studied  medicine,  then  law, 
Atty.  Gen.  U.  S.,  Minister  to  Engl,  and  Russia,  U.  S.  Senator. 

23.  John  F.  Dillon,  M.D.,LL.D.,  183 1—,  judge,  prof,  of  law  at  Columbia, 
leading  corporationist. 

24.  Launt  Thompson,  1833-94,  medical,  then  art  student,  sculptor. 

25.  J.  McNeill  Whistler,  1834-1903,  West  Pt.  1851-4,  then  artist. 

26.  William  Thornton,   1 761-1824,  physician,  first  architect  Capitol 
(D.C.) 

27.  Gen.  Isaac  Newton,  1837-84,  student  of  medicine  and  engineering, 
famous  at  latter. 

28.  William  Harkness,  M.D.,  LL.D.,   1837-1903,  astronomer,  prof, 
mathematics  U.  S.  N.,  director  U.  S.  Naval  Observatory. 

29.  Geo.  R.  Dennis,  M.D.,  1822-82,  graduate  engineer,  U.  S.  Senator, 
national  delegate,  R.  R.  president. 

30.  Wm.  S.  Haymond,  M.D.,  1825-85,  graduate  engineer,  president 
I.  D.  &  C.  RR.,  M.C.  (Ind.  1875-77),  prof,  and  dean  Ind.  Med.  Coll. 

31.  Joseph  Thomas,  A.B.,  M.D.,  181 1-91,  lexicographer,  prof,  of  Greek. 

32.  Francis  Vinton,  S.T.D.,   1809-72,  West  Pt.   1830,  lawyer,  rect. 
Trinity,  N.  Y.  C,  prof,  theology  (P.  E.) 

33.  Morgan  Dix,  D.D.,  1827-1908,  studied  law,  rector  Trinity,  N.  Y.  C. 

34.  Samuel  Seabury,  D.D.,    1729-96,  studied  medicine,  first  P.   E. 
bishop  of  Conn,  and  in  U.  S. 

35.  John  T.  Quintard,  M.D.,  D.D.,  1824-98,  prof,  physiol.,  later  P.  E. 
bishop. 

36.  Francis  S.  M.  Chatard,  M.D.,  D.D.,  1834-1918,  R.  C.  Bishop. 

37.  Wm.  B.  Stevens,  M.D.,  D.D.,  1813-87,  P.  E.  bishop  of  Pa. 

38.  Edward  Thompson,  M.D.,  D.D.,  1810-70,  bishop,  presdt.  Ohio 
Wesl.  Univ. 

39.  Isaac  W.  Wiley,  M.D.,  D.D.,  1825-84,  editor,  M.  E.  bishop. 

40.  George  Upfold,  M.D.,  1 796-1 872,  first  P.  E.  bishop  of  Ind. 

41.  Matthew  Simpson,  M.D.,  D.D.,  181 1-84,  M.  E.  bishop. 

42.  E.  S.  Janes,  M.D.,  D.D.,  1807-76,  M.  E.  bishop. 

43.  Henry  U.  Onderdonk,  M.D.,  D.D.,  1 789-1 858,  P.  E.  bishop  of  Pa. 

44.  Thomas  A.  Starkey,  D.D.,  1824-1903,  civil  engineer,  P.  E.  bishop 
No.  N.  J. 

45.  Luther  B.  Wilson,  M.D.,  D.D.,   1856-    ,  M.E.  bishop,  president 
Am.  Anti-Saloon  League,  College  trustee. 


886  SOURCES  OF  INTELLECTUAL  POWER 

Many  of  the  most  distinguished  of  our  early  clergy  had  a  medical 
as  well  as  theological  training,  and  hence  can  be  cited  collectively 
in  illustration.  And  nearly  all  the  more  prominent  medical  mission- 
aries, a  long  list,  have  also  had  a  theological  schooling. 

The  many  medical  men  who  in  the  past  did  so  much  in  the 
sciences  of  chemistry,  botany,  and  biology  can  be  regarded  either 
as  doubly  trained  or  as  simply  adopting  an  allied  specialty.  Geolo- 
gists are,  however,  so  far  afield  as  to  be  illustrative  of  this  form  of 
double  life.  In  the  list  are  such  names  as,  John  S.  Newberry,  M.D., 
LL.D.,  1822-92;  T.  Sterry  Hunt,  1826-92,  John  Locke,  M.D., 
1 792- 1 856;  Wm.  W.  Mather,  LL.D.,  1804-59,  West  Pt.  1828; 
F.  V.  Hayden,  M.D.,  LL.D.,  1829-87;  John  Evans,  M.D.,  1812-61; 
Douglas  Houghton,  M.D.,  1809-45;  B.  F.  Shumard,  M.D.,  1820- 
69;  Geo.  G.  Shumard,  M.D.,  1826-67;  David  Dale  Owen,  M.D., 
1807-60;  Richard  Owen,  M.D.,  LL.D.,  1810-90;  Chas.  A.  White, 
M.D.,  LL.D.,  1826-1912;  and  three  clergymen,  O.  W.  Wright, 
A.M.,  M.D.,  1824-88;  J.  P.  Lesley,  1819-1903;  Geo.  F.  Wright, 
D.D.,  LL.D.,  1 838-. 

A  side  illustration  to  the  same  effect  is  aflforded  by  the  members 
of  Congress  who  have  taken  both  medical  and  legal  training.  To 
19 10  there  were  at  least  fifty  such.  Many  of  these  were  prominent 
in  aflfairs  both  in  and  out  of  Congress.  Considering  there  were 
relatively  few  in  the  country  with  such  professional  doubling, 
the  number  gaining  this  mark  of  favor  is  large  enough  to  be 
notable. 

Whatever  may  be  the  case  in  other  countries,  it  is  evident 
that  in  the  U.  S.,  from  earliest  time  quite  to  the  present,  this  form 
of  education  has  yielded  admirable  results.  That  some  of  these 
men  had  a  collegiate  course  as  well,  or  other  elements  of  inheritance 
or  surroundings,  does  not  aff"ect  the  bearing  of  the  facts  shown. 
The  medical  may  be  the  best  primary  or  alternate  training,  though 
any  excess  of  medical  names  in  the  lists  is  as  much  due  to  the  kind 
of  biographic  material  accessible. 

The  above  is  a  sufficiently  striking  presentation,  though  only  of 
a  few  names  at  hand.  Its  relative  importance  is  enhanced  many 
fold  by  the  fact  that  this  educational  course  has  always  been  the 
exception.  If,  under  such  circumstances,  and  with  strong  prejudices 
to  dispirit  and  oppose  them,  its  votaries  make  so  excellent  a  showing. 


SOURCES  OF  INTELLECTUAL  POWER  887 

then  we  must  conclude  that  their  system  of  intellectual  develop- 
ment has  merit  of  a  high  order. 

Clergymen,  generals,  lawyers  and  judges,  educators,  scientists, 
journalists,  artists,  are  each  represented.  Hence  clearly  in  all  lines 
of  intellectual  importance  (unless  in  that  of  imaginative^  literature) 
the  double  scheme  works  out  well.  It  is  consequently  of  general 
worth  as  an  intellectualizer. 

It  is  evident  that  those  of  double  training  possess  a  binocular 
mentality,  and  a  correspondingly  superior  perspective  of  life. 

(6).  Migrations  oj  Students.  Exchange  of  present  or  prospective 
calling  is  not  practicable  for  the  many.  Training  can  be  varied  with 
success  for  far  larger  numbers,  and  byways  little  used  in  this  country. 
This  involves  well-tried  and  in  no  sense  experimental  methods. 

This  refers  to  students*  freedom  to  take  their  professional 
course  at  more  than  one  institution.  Often  there  is  only  a  transfer 
for  a  term  or  a  year  to  gain  instruction  not  satisfactorily  given  at 
the  primary  institution.  Other  objects  play  a  r6Ie — to  travel, 
enlarge  acquaintance,  compare  methods  and  matters  taught, 
learn  opportunities,  etc.  But  few  of  our  student  class  get  any 
timely  understanding  of  the  importance  of  this  principle,  and 
fewer  yet  are  able  to  secure  equable  permission.  Such  applicants 
are  eyed  as  shirkers  of  some  sort.  Accident  and  persistence  may 
occasionally  gain  the  chance.  To  the  routinist  this  may  seem  but 
"climbing  up  some  other  way,"  that  is  merely  because  it  is  not 
customary.  In  America  this  practice  has  had  little  vogue.  But  in 
some  countries  it  has  been  used  so  long  and  so  largely  that  its 
merits  are  beyond  question.  Possibly  it  has  not  been  favored  here 
because  it  costs  nothing;  and  as  it  carries  no  reward  there  is  no 
profit  in  advancing  it. 

No  one  who  has  not  had  experience  with  the  habit  of  student 
migration  can  have  any  appreciation  of  its  peculiar  and  rounding 
usefulness  for  the  student  himself,  and  the  healthy  stimulus  it 
gives  to  teachers  as  well.  It  is  one  of  the  few  great  principles  that 
have  given  such  impetus  to  teaching  in  the  lands  where  practiced, 
though  rarely  considered  in  discussions  by  our  educators. 

*  In  the  case  of  fictionists  variation,  similar  to  that  above  seen  in  formal  education, 
may  be  of  other  origin,  as  from  travel,  personal  experience,  or  inheritance.  Someone 
has  shown  that  poets  are  of  mixed  racial  stock,  thus  establishing  for  them  an  analogous 
equivalent  due  to  heredity. 


888  SOURCES  OF  INTELLECTUAL  POWER 

As  a  recent  writer  says:  "The  faculties  of  our  universities  are 
undoubtedly  too  immobile."^  Change  his  word,  "faculties"  to 
read  "students,"  and  it  applies  here.  To  make  faculties  move  or  mix 
involves  vast  trouble;  students  will  move  themselves,  if  freely 
permitted. 

Exchange  professorships  are  fine  courtesies  and  have  a  place. 
But,  as  occupants  with  technical  outfits  can  hardly  carry  every- 
thing with  them,  it  is  not  an  exchange  in  any  full  sense,  and  must 
be  limited  either  to  those  not  so  encumbered  or  be  but  a  special 
performance.  However  valuable,  the  scheme  does  not  give  much 
added  scope  or  choice  for  students. 

On  the  other  hand,  the  principle  of  exchange  can  be  extended 
to  all  students.  There  might  even  be  exchange-studentships.  For 
scholar  and  professor  alike  it  is  good  to  have  an  open  chance, 
information  as  to  how  to  work  out  his  own  salvation,  and  the 
prospect  of  gaining  a  meed  of  recognition. 

No  medical  man  in  the  recent  annals  of  this  country  has  been 
so  keen  to  award  recognition  to  both  friend  and  stranger  as  the 
dedicatee  of  this  work,  one  of  his  little-noted  services  to  American 
medicine.  Some  scheme  is  certainly  desirable  for  animating  students 
who  en  masse  too  often  feel  like  "dumb  driven  cattle." 

Elective  courses  do  not  offer  much  variety  in  the  present  sense, 
nor  can  they  find  a  ready  place  in  professional  schools. 

Neither  is  it  met  by  scholarships,  fellowships,  or  other  stipends, 
barring  the  traveling  kind.  At  most  these  are  for  the  few,  and 
afford  no  solution  for  the  great  body  of  students.  And,  regarding 
the  selected  holders  of  these  billets,  the  Biblical  adjuration  about 
the  stone  that  the  builders  rejected  is,  as  every  observer  well  knows, 
quite  as  true  now  as  in  early  times. 

The  development  of  graduate  opportunities  oflfers  a  solution, 
though  belated  as  regards  the  individual,  and  only  for  such  as 
can  afford  more  extended  study.  If  the  present  talk  of  economy 
applies  to  education,  here  is  a  chance  by  better  use  of  undergraduate 
time.  For  any  adequate  plan  adapted  to  general  needs  we  can 
consequently  but  come  back  to  that  of  student  migrations  as  the 
best,  the  fairest  that  the  world  has  so  far  devised.  The  change 
privilege  might  be  given  as  a  reward  to  those  above  a  certain 

*  Nutting,  in  Science,  19 18,  December  20. 


SOURCES  OF  INTELLECTUAL  POWER  889 

standard  of  scholarship,  were  it  not  that  the  laggard  is  the  one 
most  in  need  of  stimulus. 

In  no  case,  as  it  works  out  in  practice,  are  a  majority  of  the 
students  ever  at  one  time  away  from  their  favorite  institution. 
And  those  who  stay  at  one  place  for  their  whole  course  get  benefit 
by  association  with  those  who  do  make  use  of  the  privilege; 
information  is  continually  exchanged  with  those  from  other  seats. 
For  its  patrons  it  insures  a  more  intimate  acquaintance  with  each 
center  and  its  student-life  than  does  either  of  the  substitute  propo- 
sitions. It  adds  in  all  these  ways  greatly  to  the  intellectual  progress 
of  the  whole  student  body.  The  long  distances  that  many  of  our 
students  have  to  travel  to  reach  their  professional  schools  would 
not  be  materially  affected  by  such  modification  of  custom.  The 
remoteness  of  many  such  institutions  from  one  another  may  oftener 
be  a  handicap,  but  would  make  little  difference  to  the  enthusiasm 
of  our  youth. 

To  account  for  this  lack  of  opportunity  with  us,  there  is  of 
course  a  shift  of  reasons.  It  is  said  by  some  of  our  university  men 
that  any  such  freedom  is  incompatible  with  the  American  system — 
simply  a  form  of  gentle  evasion.  Another  time  it  is  claimed  that 
only  a  strongly  centralized  power  can  do  anything — also  to  be 
taken  with  allowance,  as  any  State  or  school  can  start  the  work  for 
itself  and  accomplish  something. 

The  lethargy  of  a  petrified  relic  comes  nearer  to  the  real  reason. 
In  the  early  years  of  all  our  professional  schools,  as  soon  as  a  student 
matriculated  he  was  viewed  as  a  financial  resource.  This  old  way 
of  regarding  students,  and  as  a  result  their  habits  of  procedure,  still 
persists.  In  fact  all  the  schools  continue  to  find  a  use  for  their  student 
fees,  and  where  this  necessity  is  at  all  relaxed  there  comes  the 
desire  for  its  prestige  to  score  as  big  a  roster  of  students  as  possible. 
Consequently  former  ideas  and  customs  still  hold  sway.  In  fact, 
without  some  degree  of  enlightenment  as  to  the  value  and  uses  of 
the  privilege,  loosening  the  strings  might  have  little  more  effect 
on  our  students  than  lifting  the  bars  about  long-caged  animals. 
Time  would  serve  to  correct  this. 

It  can  be  realized  in  one  of  two  ways.  Any  school  can  offer 
permission  to  its  students,  merely  requiring  satisfactory  certification 
of  study  elsewhere.  In  a  sense  this  is  now  possible,  but  the  impedi- 


9^  SOURCES  OF  INTELLECTUAL  POWER 

ments  everywhere  placed  in  the  way  are  so  troublesome,  and  co- 
operation, or  practically  unionism,  is  applied  with  such  effect 
that  rarely  does  a  student  attempt  change,  unless  compelled  by 
circumstances. 

The  other  plan  must  await  the  extension  of  inter-collegiate 
examining  work  from  the  present  entrance  tests  to  the  later  stages 
of  training.  When  that  extension  of  university  methods  is  realized, 
this  desideratum  may  find  its  natural  fulfillment.  There  will  still 
remain  the  wider  ideal  of  its  extension  between  accredited  nations. 

What  objections?  None  that  is  valid.  Migrations  do  not  inter- 
fere with  systematic  study  or  teaching.  Students  can  remain  at 
any  preferred  place,  and  graduate  where  they  like.  This  involves 
no  outlay  by  institutions,  nor  does  it  lengthen  the  time  of  study. 

The  only  apparent  criticisms  are:  Possibly  a  slight  amount  of 
clerical  trouble  in  giving  certificates  for  work  accomplished.  And 
an  maginary  loosening  of  alumni  attachment.  In  practice  this 
latter  does  not  seem  to  materialize.  Either  the  present  system  chafes 
many  excellent  students,  or  for  whatever  reason  the  attachment 
of  a  goodly  proportion  of  our  alumni  ceases  at  graduation.  By  the 
liberal  system  a  deeper  appreciation  of  the  educational  parent  is 
often  engendered.  The  balance  is  rather  in  favor  of  migratory 
permission, — better  trained,  better  satisfied,  and  hence  more 
devoted  and  more  available  graduates. 

The  advantages  of  student  migration  include  such  matters  as: 

1.  Enlarged  acquaintance  with  conditions,  teachers  and  fellow- 
students,  especially  those  who  are  to  be  future  colleagues  in  life. 

2.  A  rounding  out  of  studies  by  choice  of  opportunities. 

3.  Greater  variety  in  social  experience  and  in  training,  with 
relief  of  the  narrowness  so  common  at  single  schools. 

4.  The  enormous  stimulus  to  and  broadening  of  the  teachers 
themselves. 

5.  The  bringing  back  of  added  spirit  and  of  common  information, 
in  the  usual  cases  of  return  to  the  former  place,  or  by  new  students 
from  other  places. 

The  value  of  variation  in  mental  training,  as  an  aid  to  intellectual 
development,  can  be  traced  in  many  directions,  though  not  often 
with  any  degree  of  exactness  if  even  of  certainty.  To  attempt  this, 
two  definite  and  determinable  types  have  here  been  considered.  These 


SOURCES  OF  INTELLECTUAL  POWER  891 

are  so  similar  in  character  that  the  first  or  larger  (educationally, 
not  numerically)  includes  the  second  or  smaller;  and  the  latter  rests 
on  its  own  basis  as  well. 

Of  the  two  sources  outlined,  it  is  not  necessary  for  present 
purposes  to  decide  whether  the  former  is  due  to  inheritance  of 
acquired  characteristics,  to  the  gradual  accumulation  of  family 
tradition,  education,  and  opportunities,  or  to  other  technical 
cause.  The  pragmatic  conclusion  holds,  that  medical  heredity  is 
one  of  the  best  sources.  Like  most  hereditary  factors  in  the  human, 
it  can  hardly  be  made  of  direct  use,  but  may  have  the  more 
theoretical  and  historical  interest. 

The  second  source,  on  the  contrary,  adds  little  on  the  side  of 
theory,  but,  like  all  environmental  elements,  offers  something 
available,  and  carries  with  it  its  own  lessons  for  students  them- 
selves and  their  sponsors. 


THE  PSYCHOLOGY  OF  ANTICIPATION  AND  OF 

DREAMS 

By  Frederick  Peterson,  M.D.,  New  York 

THE  thread  of  thought,  the  train  of  ideas,  the  stream  of  con- 
sciousness, are  familiar  phrases  in  psychology.  On  the  thread 
of  thought  are  strung  the  past,  the  present,  and  the  future. 
On  the  train  of  ideas  we  leave  one  coast  behind  for  the  coast  that  lies 
far  ahead.  The  stream  of  consciousness  flows  from  the  reservoir  of 
memory  across  the  present  into  the  unknown  to  some  distant  sea. 

The  books  on  psychology  tell  us  much  of  memory  and  of  the 
action  of  mind  in  the  present,  of  volition,  attention,  judgment, 
emotion,  association,  concepts,  instinct,  perceptions,  but  they  tell 
us  very  little  of  the  relation  of  that  stream  of  consciousness  to  the 
future.  Nevertheless,  the  essential  function  of  the  mind  is  its  dealing 
with  the  future.  Anticipation  of  the  future  is  the  light  that  guides  our 
conduct,  which  plans  and  chooses,  which  distinguishes  the  right 
from  the  wrong  paths  that  we  are  to  follow,  and  the  ways  that  are 
favorable  to  progress  from  those  that  are  unfavorable.  Our  memories 
are  our  experience,  the  present  is  a  point,  the  future  is  everything. 
In  youth  especially  the  preoccupation  of  the  mind  is  almost  wholly 
with  what  is  to  come.  In  old  age  which  has  no  future  the  predilection 
is  for  the  past.  Childhood  and  adolescence  are  one  long  preparation 
for  the  future,  groping,  seeking,  planning,  foreseeing.  The  education 
of  our  young  people  is  not  so  much  a  drawing  out  of  latent  faculties 
as  a  filling  in  of  the  mind  with  the  kind  of  knowledge  and  experience 
that  shall  determine  future  conduct,  foreshadow  the  events  that 
are  to  be,  choose  the  best  in  ambition  and  endeavor. 

It  is  not  that  the  future  in  mental  function  is  so  much  concerned 
with  prophecy,  augury,  premonition,  presentiment,  soothsaying, 
clairvoyance,  horoscopes,  or  even  astronomical  prediction,  but  that 
it  enters  into  the  very  psychology  of  our  everyday  life.  This  is 
abundantly  shown  by  the  richness  of  language  in  words  involving 
the  element  of  futurity,  such  as  foreboding,  forethought,  foreordain, 
forecast,  forewarn,  foresight,  foretaste,  foreknown,  presage,  predis- 
position, prevision,  provision,  providence,  prospect,  prescience,  pre- 

892 


PSYCHOLOGY  OF  ANTICIPATION  AND  DREAMS    893 

determine,  premeditate,  divination,  auspices.  These  are  some  of 
many  markedly  futuristic  words,  but  the  same  element  of  futurity  is 
present  in  countless  other  words,  such  as  expect,  intention,  specula- 
tion, design,  resolve,  plan,  provide,  problem,  solution,  preparation, 
rehearse,  discern,  training,  evolve,  surmise,  prudence,  sagacity, 
dehberation,  counsel,  fate,  advise,  promise,  calculation,  announce, 
explore,  menace,  likelihood,  curiosity,  destiny,  and  the  hke. 

All  of  our  hopes,  desires,  wishes,  drives,  trends,  tendencies,  pro- 
pensities, needs,  longings,  cravings,  ambitions,  and  aspirations — 
as  well  as  our  timidities,  anxieties,  suspense,  surprise,  dreads,  and 
fears — have  to  do  with  this  same  element  of  anticipation.  Yet  the 
academic  psychologies  scarcely  mention  the  future  with  the  excep- 
tion of  an  occasional  paragraph  on  expectant  attention.  We  have 
need  now  of  a  new  study  of  the  psychology  of  anticipation. 

The  sculptor  prefigures  in  the  block  of  marble  some  divine 
creation.  The  painter  with  his  palette  of  colors  and  stretch  of 
canvas  foresees  the  whole  to  which  laborious  days  will  bring  fruition. 
The  speculator  and  politician  devise  their  schemes  for  success  on 
weil-Iaid  plans  for  the  far-distant  future.  The  whole  life  of  the 
growing  child  is  preparation  for  the  work  of  life,  with  days  full  of 
joyous  anticipations  of  pleasures  to  come,  laying  in  stores  for  future 
use,  and  hours  sometimes  tinged  with  little  worries  over  the  future, 
or  with  apprehensions  for  misdeeds  punishable  by  parent  or  teacher, 
or  with  occasional  fears  born  of  reprimand,  or  of  unwholesome 
stories.  The  stream  of  consciousness  in  the  scientist  busied  with 
some  burning  problem  stretches  far  out  into  the  unknown  yet  sur- 
mised beyond.  What  vast  horizons  beckon  to  the  philosopher  who 
reaches  with  his  antennae  of  ideas  into  the  void  of  space  and  coming 
timel  Even  I,  who  occupy  my  days  with  patients,  busy  myself  with 
their  hopes  and  fears  and  with  the  prognosis,  and  among  my 
recreations  watch  with  expectant  attention  my  growing  crops  and 
increasing  flock  of  Dorsets;  while  on  journeys  to  and  from  the  farm  I 
read  detective  stories,  planned  by  expert  writers  to  keep  me  always 
in  the  condition  of  alert  anticipation  as  to  what  comes  next.  Every 
novehst  writes  for  the  anticipation  of  his  readers,  and  every  reader 
is  leaping  forward  to  the  climax  of  the  story  with  his  faculty  of 
expectation.  When  the  gifted  orator  on  the  platform  is  expounding 
his  experience  or  solving  his  problem,  the  attentive  listener  not 


894   PSYCHOLOGY  OF  ANTICIPATION  AND  DREAMS 

only  follows  his  line  of  argument,  but  pushes  forward  to  the  cul- 
mination often  before  the  speaker  gets  there  himself.  In  an  extem- 
poraneous address,  especially  if  given  in  a  foreign  anguage,  in  which 
one  is  not  altogether  fluent,  the  speaker's  own  thoughts  as  well  as 
those  of  his  hearers  are  always  running  ahead  of  his  laborious 
expression.  In  listening  to  music,  the  mind  of  the  listener  is  con- 
stantly anticipating  the  coming  changes  of  harmony,  the  return  of 
phrase  and  motif.  The  fears,  suspicions,  anxiety,  hopelessness  of 
many  morbid  mental  states  are  in  reality  a  disorder  of  the  faculty  of 
anticipation. 

Now  since  we  live  in  a  world  of  common  sense  and  practical 
realities,  let  us  see  how  this  view  of  the  stream  of  consciousness 
applies  to  dreams,  which,  grotesque  and  bizarre  as  they  generally  are, 
still  belong  to  our  world  of  reahties,  even  if  a  sort  of  underworld  of 
realities. 

Bergson  compares  our  store  of  memories  to  a  pyramid  whose 
p)oint  is  inserted  precisely  into  our  present  action.  We  might  perhaps 
compare  the  mind  to  a  fountain  pen  filled  with  experience,  with  its 
point  of  the  present  poised  and  ready  to  write  upon  the  white  tablet 
of  the  future. 

In  conscious  and  directed  thought  we  draw  upon  a  very  limited 
store  of  memories,  but  dreams  often  seem  to  release  and  use  the 
whole.  The  day  dream,  the  undirected  stream  of  thought,  the  idle 
drift  of  fancy  or  phantasy,  with  its  relaxation  of  control,  lies  between 
directed  thought  and  dream,  and  is  usually  concerned  with  pleasant 
anticipation  or  agreeable  reminiscence  in  a  comfortable  state  of  mind 
and  body.  (There  is  little  day  dreaming  among  those  suffering  from 
physical  distress  or  care,  worry,  and  anxiety.) 

Even  the  concentration  of  directed  thought  is  subject  to  intru- 
sions of  more  or  less  irrelevant  fringes  of  other  chains  of  associations 
or  occasional  saltatory  ideas.  In  day  dreams  the  looseness  of  con- 
catenation lends  itself  still  more  to  such  intrusion  and  incoher- 
ence. In  the  dreams  of  sleep  there  is  still  greater  relaxation  of 
direction,  all  the  doors  of  memory  are  unlocked,  flung  wide,  the 
countless  strands  of  associations  are  rewoven  in  kaleidoscopic  pat- 
terns, with  all  sorts  of  intrusions,  auto-suggestions,  and  immediate 
suggestions  from  the  more  or  less  active  sensory  apparatus  of  the 
body,  all  played  with  by  reminiscence  and  anticipation.  The  antici- 


PSYCHOLOGY  OF  ANTICIPATION  AND  DREAMS    895 

pations  may  be  disagreeable  and  painful  or  agreeable  and  pleasant, 
and  the  dreams  correspondently  occupied  with  subjects  of  apprehen- 
sion, fear  and  terror,  or  of  hopes,  wishes,  and  desires.  The  currents  of 
dream  consciousness  would  seem  to  be  a  kind  of  reflection  of  the 
currents  of  alert  consciousness,  a  moonlit  underworld  of  daily  com- 
mon life,  with  wider  horizons  as  to  past  and  future,  without  the 
tension  of  directing  and  choosing,  though  not  wholly  "disinterested," 
as  Bergson  would  have  it,  with  a  looser  mesh  of  association,  and  wide 
open  to  suggestion  from  any  source,  either  in  the  flowing  stream  of  the 
unconscious  mind  or  in  the  sensitive  body  that  houses  the  mind. 

One  of  the  amazing  features  of  dreams  to  many  is  the  tendency 
to  tell  a  story,  to  dramatize,  or  even  as  in  the  case  of  Coleridge  to 
write  a  complete  poem  (Kublai  Khan).  Robert  Louis  Stevenson,  in 
his  "Chapter  on  Dreams,"  gives  us  a  very  good  picture  of  the  child 
with  night-terrors  and  nightmares  made  up  for  the  most  part  of  a 
confounding  of  his  everyday  school  troubles  and  tasks  with  the 
"ultimate  and  airy  troubles  of  hell  and  judgment,"  which  later  grew 
with  his  dawning  outlook  on  the  great  world  and  his  increasing 
knowledge  and  aspirations  into  quiet  anticipatory  dreams  of 
journeys  to  strange  towns  and  beautiful  places  with  adventures;  and 
presently  he  began  making  stories  in  his  dreams;  and  later  to  write 
them  out  and  sell  them  like  the  thrifty  Scotchman  that  he  was. 

Dramatization  in  dreams  is  probably  not  unusual,  and  depends 
upon  that  same  anticipatory  faculty  which  leads  the  novelist  on  with 
his  story  and  his  reader  to  go  far  in  advance  of  the  novelist's  pages. 
A  thought,  a  sensation,  a  picture,  or  a  sound  in  the  dreamer  starts 
up  an  anticipatory  idea  and  this  another  until  the  plot  is  woven. 
On  a  steamer  coming  home  from  China  I  suddenly  woke  one  night  and 
wrote  down  at  once  this  nonsense  jingle  that  I  had  just  dreamed: 

Said  Zambo-Ango 
"Where  is  my  bango?" 
And  Whango  said 

1  am. 
Said  Zambo-Ango 
"You  rotten  mango 
I'll  kick  you  to  Siam." 
And  Whango  said 
"Go  damn." 


896   PSYCHOLOGY  OF  ANTICIPATION  AND  DREAMS 

I  had  probably  seen  the  rather  amusing  name  of  the  town  Zamboanga 
on  a  map  of  the  Philippines,  and  with  a  tendency  to  rhyming,  the 
word  in  the  dream  suggested  by  anticipation  one  rhyme  and  idea 
after  the  other  in  the  order  quoted.  Of  course  the  anticipatory 
faculty  would  be  nothing  without  memories  and  experience.  These 
are  naturally  drawn  upon  for  the  development  of  the  projected 
sequence.  How  this  is  accomplished  and  why  dreams  exhibit  often 
so  much  incongruity  and  incoherence  is  well  presented  by  Bergson. 
Suppose  there  should  arise  in  the  visual  field  of  the  dreamer  a  green 
spot  w;ith  white  points.  Very  different  memories  might  be  summoned 
by  this  sensation — a  lawn  with  white  flowers  or  a  billiard  table  with 
balls  or  a  host  of  other  things  besides,  and  one  of  these  may  pass 
into  the  other.  I  recently  had  an  experience  of  this  kind.  I  went  to 
sleep  on  a  sofa  looking  into  a  round  mass  of  red  embers  in  the  fire- 
place. I  dreamed  a  dog  was  coming  toward  me  with  one  great 
blazing  red  eye.  At  first,  a  little  alarmed,  I  remembered  it  must  be 
my  Airedale  asleep  on  the  rug  by  the  fire.  Immediately  a  bare  arm 
appeared  before  me  with  a  round  fresh  vaccination  mark,  bleeding. 
Both  dreams  were  evidently  based  upon  visual  after-images  of  the 
heap  of  glowing  coals. 

Anticipation  utilizes  the  material  of  past  experience  much  as 
is  done  in  the  construction  of  the  cantilever  bridge,  where  suitable 
material  is  brought  up  piece  by  piece,  fragment  by  fragment,  from 
behind  and  pushed  forward  and  fitted  into  the  extending  arch  until 
the  whole  aerial  span  is  finished.  When  dreams  are  dramatized  there 
is  no  failure  of  interest  in  the  plot.  It  is  not  quite  a  "disinterested" 
process. 

In  recent  years  much  has  been  published  on  the  Freud  theory 
of  dreams.  It  would  seem  that  Freud  in  meditating  on  the  un- 
conscious was  much  struck  with  the  dreams  of  his  children,  which 
doubtless  were  busied  chiefly  with  joyous  anticipations  of  days  in 
the  country,  trips  to  the  Prater,  toys,  theaters,  jollifications,  and  it 
quite  naturally  occurred  to  him  in  this  connection  that  some  dreams 
might  be  the  "fulfillment  of  a  wish."  It  was  a  saltatory  idea  that  took 
complete  possession  of  him,  and  before  long  he  announced  in  a  book 
the  hypothesis  that  all  dreams  are  "the  fulfillment  of  a  wish." 
Every  dream  henceforth  had  to  be  interpreted  in  accord  with  his 
anticipatory  desire  to  find  a  wish-fulfillment. 


PSYCHOLOGY  OF  ANTICIPATION  AND  DREAMS     897 

The  difficulties  proved  very  great,  but  if  one  is  sincerely  bent 
upon  discovering  ciphers  in  Shakespeare  there  is  always  some 
Ignatius  Donnelly  to  do  it.  As  so  many  dreams  present  painful  or 
distressing  contents,  fears,  and  so  on,  among  their  anticipations, 
reflecting  the  tendencies  of  normal  waking  thought,  it  was  necessary 
to  invent  something  entirely  new  and  quite  at  variance  with  usual 
conscious  thought  processes  to  support  the  Freudian  preconception. 
If  after  reading  his  book  you  have  a  fear  dream,  the  concealed  wish 
is  very  clear  as  a  desire  to  confute  Freud.  (He  gives  instances  of 
this  in  his  book.)  When  the  wish  is  not  as  manifest  as  this,  one  has 
recourse  to  the  "latent  dream  content"  with  such  remarkable 
"distortion"  and  "displacement"  that  only  Freud  and  his  followers 
can  interpret  it  properly.  The  "dream  censor"  is  evoked  with  his 
unpleasant  faculty  of  "disfiguring"  or  "disguising"  the  dream- 
contents  in  order  to  conceal  the  real  wish  of  the  dreamer  from  any 
but  the  analyst.  Thus  the  formula  for  the  interpretation  of  fear  and 
anxiety  dreams,  which  by  common-sense  explanation  would  simply 
reflect  in  a  measure  such  fears  and  anxieties  as  we  often  have  in  our 
conscious  Hfe,  is  to  quote  Freud.  Such  dreams  are  "the  disguised 
fulfillment  of  a  suppressed  or  repressed  wish,"  and  "the  content  of 
fear  and  anxiety  dreams  is  of  a  sexual  nature,  the  Hbido  belonging  to 
which  content  has  been  transformed  into  fear." 

A  neurotic  young  lady,  a  patient  of  mine,  often  has  a  fear  dream 
as  follows:  She  dreams  she  is  awakened  by  the  house  being  on  fire 
and  she  runs  from  the  house  in  a  panic  scantily  attired.  A  Freudian 
interpretation  would  be  easy  and  clear — and  yet  very  far  from  the 
fact.  On  two  occasions  the  country  houses  in  which  she  Hved  did 
actually  catch  fire  in  the  night  and  burn  to  the  ground,  and  she  ran 
from  the  house  on  each  occasion  in  a  state  of  panic  scantily  clothed. 

The  extraordinary  symbofism  ascribed  to  dream-life  by  the 
"new  psychology"  is  chiefly  the  invention  of  the  psychanalysts. 
There  is  probably  Httle  in  the  subconscious  or  unconscious  mind  of 
any  individual  that  has  not  at  some  time  been  conscious,  and  there 
can  be  no  symbols  there  which  have  not  been  at  some  time  symbols 
in  waking  thought.  Most  of  the  symbolism  described  by  the  new  in- 
terpreters of  dreams  reflects  the  symbofism  of  the  analysts  them- 
selves. In  fact  there  is  more  to  be  learned  from  the  interpretations 
pubfished  of  the  psychology  of  the  analyst  than  of  the  psychology  of 


898    PSYCHOLOGY  OF  ANTICIPATION  AND  DREAMS 

the  dreamer.  The  analyst  reveals  himself  in  his  analysis,  his  anticipa- 
tions, his  intelligence,  his  learning,  his  logic,  and  his  wish,  for  if 
there  is  any  wish  brought  clearly  to  light  in  the  analysis  it  is  that 
of  the  interpreter;  and  the  theoretical  "distortion,"  "displacement," 
and  "disfigurement"  ascribed  to  dreams  in  "the  new  psychology" 
become  actualities  in  the  analytic  story. 

To  the  Freudian  there  is  but  one  drive,  the  sexual,  and  to  him 
all  the  arts  and  accomplishments  of  civihzation  are  but  the  sublima- 
tion of  that.  This  is  a  Rabelaisian  theory.  It  will  be  remembered 
that  Pantagruel  in  his  travels  met  one  Caster  by  name,  who  con- 
sidered all  the  powers  and  attainments  of  man  to  be  the  sublimation 
of  the  desires  of  the  stomach. 

In  reality  there  are  many  powerful  drives  besides  those  of  sex 
and  hunger,  well  described  by  Woodworth  in  his  "Dynamic  Psy- 
chology," among  which  may  be  mentioned  fear,  disgust,  curiosity, 
anger,  self-assertion,  submission,  the  gregarious  instinct,  the  in- 
stincts of  construction  and  acquisition,  imitation,  suggestibility, 
play-instinct,  and  all  the  later  acquired  drives  determined  by  special 
gifts  and  aptitudes  in  the  great  workshop  of  the  world,  and  our 
absorption  in  our  particular  interests  there.  Individual  development 
is  one  long  series  of  "preparatory"  or  anticipatory  reactions  for  the 
"consummatory"  reactions  that  are  to  follow.  It  would  seem  as 
though  sex  and  hunger  play  a  secondary  part  in  the  behavior  of 
mankind  in  general.  Survival  and  reproduction  are  necessary  to 
man's  advance  as  conqueror  of  his  environment,  but  the  goal  of  his 
ultimate  consummatory  reaction  is  the  encompassing  by  his  brain 
and  mind  of  the  planet  and  the  stars. 

What  has  been  said  of  the  faculty  of  anticipation  in  our  mental 
processes  is  in  a  measure  paralleled  in  our  physiological  and  morpho- 
logical makeup.  Sherrington  has  pointed  out  how  the  special  sensory 
apparatus  of  the  "leading  segments,"  the  "distance-receptors" 
(nose,  eyes,  ears)  in  biological  evolution,  have  contributed  most  to 
the  uprearing  of  the  cerebrum,  extending  the  powers  of  investigating 
the  environment,  projecting  the  creature  into  wider  horizons. 

Feeding  and  reproduction,  necessary  but  subsidiary  functions 
of  our  being,  are  relegated  to  the  lower  segmental  levels.  In  the 
leading  segments  lie  these  sensory  distance-receptors  which  have 
made  possible  the  anticipating,  curious,  and  exploring  mind,  eager  to 
know  and  dominate  the  universe. 


r 


CLINICAL  AND  DEVELOPMENTAL  STUDY  OF  A 
CASE  OF  RUPTURED  ANEURYSM  OF  THE  RIGHT 
ANTERIOR  AORTIC  SINUS  OF  VALSALVA 

LEADING  TO  COMMUNICATION  BETWEEN  THE  AORTA  AND  BASE 
OF  THE  RIGHT  VENTRICLE,  DIAGNOSED  DURING  LIFE.  OPEN- 
ING IN  ANTERIOR  INTERVENTRICULAR  SEPTUM  (PROBABLY 
BULBAR   SEPTAL   DEFECT).   MALIGNANT   ENDOCARDITIS^ 

By  Maude  E.  Abbott,  B.A.,  M.D., 

Curator  of  the  Medical  Museums,  McGill  University,  Montreal 
(From  the  medical  wards  of  the  Royal  Victoria  Hospital) 

A  BNORMAL  communications  between  the  aorta  and  base 
Ai\  of  the  right  ventricle,  or  between  aorta  and  pulmonary 
jL  JLartery,  are  of  not  very  infrequent  occurrence.  The  event 
is  accompanied  in  the  great  majority  of  cases  by  characteristic 
symptoms,  and  signs  so  striking  as  to  be  pathognomonic.  In  a 
few  of  the  cases  the  communication  is  of  congenital  origin,  and  the 
chnical  evidences  of  its  presence  have  existed  throughout  life;  but 
in  far  the  greater  number  it  is  formed  by  the  sudden  bursting  of  an 
aneurysm  of  the  base  of  the  aorta  into  the  pulmonic  circulation, 
and  symptoms  then  set  in  suddenly.  Such  aneurysms  may  be  of  the 
so-called  "spontaneous"  type,  in  which  the  wall  of  the  ascending 
aorta  is  extensively  diseased,  from  luetic  or  other  causes.  There  is, 
however,  an  extremely  interesting  group  of  cases  in  which  the 
aortic  wall  is  perfectly  healthy,  and  the  right  anterior  aortic  sinus 
of  Valsalva  is  the  seat  of  an  opening  leading  into  a  finger  or  thimble- 
like process  which  projects  into  the  conus  of  the  right  ventricle  and 
represents  an  aneurysm  of  its  wall  and  that  of  the  aortic  sinus, 
due  not  to  disease,  but  apparently  to  a  congenital  thinning  of  the 
septum  between  the  two  great  trunks.  This  was  evidently  so,  and 
is  the  explanation  put  forward  in  the  cases  of  Beck,  (i)  Hale-White, 
(2)  Krzywicki,  (3)  and  Kraus,  (4)  in  which  the  walls  of  the  aneurysm 

*  The  anatomical  portion  of  the  study  of  this  case  was  made  under  a  grant  from  the 
Cooper  Fund  for  Medical  Research. 

899 


900  RUPTURED   ANEURYSM 

were  thin  and  membranous,  without  sign  of  inflammatory  action  of 
any  kind,  and  rupture  had  taken  place  at  the  apex  of  the  sac, 
evidently  as  a  result  of  strain.  In  the  case  of  Krzywicki  the  ven- 
tricular septum  was  entire,  but  in  the  other  three  above  cited,  and  in 
several  similar  ones  in  the  literature  (Hart,(5)  Thurnam,(6))  in  which 
the  conditions  were  obscured  (as  in  our  own  case)  by  the  existence 
of  a  malignant  endocarditis,  the  aneurysm  of  the  right  aortic  sinus 
was  associated  with  a  defect  of  the  anterior  interventricular  septum 
immediately  below  the  cusp,  in  a  situation  identical  with  that  of  the 
interventricular  communication  in  the  case  which  it  is  our  privilege 
to  report  here,  and  both  conditions  were  ascribed  by  those  who 
recorded  them  to  a  defective  development  of  the  aortic  (bulbar) 
septum  at  this  point. 

The  chnical  features  of  abnormal  communications  between  the 
aorta  and  pulmonary  circulation  were  clearly  outlined  by  Thurnam  (6) 
in  1 840,  who  reported  i  case  of  ruptured  right  aortic  sinus  aneurysm 
(summarized  below),  and  mentioned  5  others  within  his  knowledge 
in  which  a  thin-walled  membranous  sac  projected  into  the  right 
ventricle,  but  was  not  ruptured;  by  Peacock (7)  in  1868,  who  included 
Thurnam's  series  in  a  review  of  17  cases  from  the  literature,  and  by 
Brocq  (8)  in  1886.  In  all  the  cases  except  4  cited  by  these  authors  the 
communication  was  "accidental,"  due  to  rupture  of  a  "spontaneous" 
aneurysm  of  a  diseased  aortic  wall;  of  the  other  4,  which  were  all 
believed  to  be  of  congenital  origin,  2,  i  by  Thurnam,  (6)  and  i  by 
Rickards,  (9)  were  cases  respectively  of  ruptured  aneurysm  of  the 
right  aortic  sinus,  and  congenital  opening  in  this  situation.  In  the 
other  two  by  Wilks,  (10)  and  Baginsky,  (i  i)  a  smooth-walled  aperture 
of  communication  between  the  aortic  and  pulmonary  trunks  lies  above 
the  valves  but  below  the  origin  of  the  innominate  artery  (thus 
excluding  patent  ductus),  and  represents  a  defect  at  the  upper  part 
of  the  aortic  septum.  (See  Plate  IV,  S.  a.  p.)  Similar  cases  of  con- 
genital perforation  at  this  point  above  the  valves  were  reported  by 
Frantzel,  (12)  1868,  Girard,  (13)  1895,  and  Hektoen,  (14)  1900,  who 
adds  a  valuable  developmental  study  of  aortico-pulmonary  commu- 
nications of  congenital  origin.  He  quotes  a  case  by  Charteris  (15)  of 
much  interest  in  relation  to  the  subject  of  this  article,  in  which  a  hole 
behind  the  right  aortic  cusp  leads  directly  into  the  base  of  the  right 
ventricle  without  any  sign  of  aneurysm  or  inflammatory  action,  evi- 


Fig.  I.  Aneurysm  of  Right  Aortic  Sinus  of  Valsalva,  Rupturing  into  Right 
Ventricle  at  Level  of  Pulmonary  Valves. 

Associated  with  Opening  in  Anterior  Part  of  Interventricular  Septum  Leading  into 
Conus  Arteriosus  of  Right  Ventricle  (probably  Bulbar  Septal  Defect).  Malignant 
Endocarditis  of  Aortic  and  Pulmonary  Valves  and  Adjacent  Endocardium.  View  from 
Left  Ventricle. 

The  Aortic  Cusps  are  seen  Thickened  and  Deformed  by  Old  Endocarditis  and  Surmounted  by  Recent 
Vegetations  with  Ulceration  of  Subjacent  Myocardium.  Two  Probes  are  Passed,  the  Upper  through  the 
Opening  in  the  Right  Aortic  Sinus,  the  Lower  through  the  Interventricular  Communication  Immediately 
below  the  Cusp,  and  are  Both  Seen  Emerpng  Close  Together  in  the  Conus  Arteriosus  of  the  Right  Ven- 
tricle. The  Interventricular  Communication  is  Seen  to  Lie  in  the  Anterior  Part  of  the  Septum  Some  Dis- 
tance in  Front  of  the  Pars  Membranacea,  and  Directly  below  the  Anterior  Half  of  the  Right  Aortic  Cusp  ia 
the  Extreme  Anterior  (Bulbar)  Part  of  the  Interventricular  Septum.  Prom  the  case  here  reiiorted. 


RUPTURED   ANEURYSM  901 

dencing  a  true  defect  at  this  point  and  not  merely  a  congenital 
thinning.  Rickards  (9)  reported  a  similar  opening  combined  with 
ventricular  septal  defect  (summarized  below)  .^ 

The  characteristic  clinical  picture  presented  may  be  summarized 
as  follows:  Dyspnoea  without  cyanosis,  precordial  vibration  and 
thrill  of  intense  purring  character,  and  loud  sawing  murmur, 
sometimes  systolic,  sometimes  diastolic,  but  usually  continuous, 
with  systolic  or  diastolic  accentuation,  and  synchronous  with  the 
thrill.  These  signs  are  diflPerentiated  from  those  of  patent  ductus 
by  their  extremely  superficial  character  relatively  to  the  chest  wall, 
and  by  their  point  of  maximum  intensity  being  definitely  at  the 
base  of  the  heart  and  over  the  middle  of  the  precordium.  In  the  very 
rare  cases  of  congenital  perforation  of  the  trunks  (Wilks,  Baginsky, 
Frantzel,  Girard,  Hektoen)  or  of  the  right  aortic  sinus  (Charteris, 
Rickards),  these  signs  were  of  course  persistent  throughout  life. 
In  the  far  commoner  ones  of  ruptured  aneurysm,  a  sudden  onset  in  a 
person  in  apparently  perfect  health  is  a  part  of  the  symptom-complex. 
The  patient  may  survive  the  rupture  for  years,  the  precordial  thrill 
and  murmur  persisting  unchanged. 

The  following  case,  which  presents  a  picture  pathognomonic 
in  all  details  of  an  aneurysm  of  the  base  of  the  aorta  rupturing  into 
the  pulmonary  artery  or  base  of  the  right  ventricle  nine  years  before 
death,  occurred  in  the  public  service  of  Dr.  W.  F.  Hamilton,  who 
kindly  accorded  to  me  the  fullest  privileges  of  observation  during 
the  nine  months  of  the  patient's  stay  in  the  hospital,  and  gave  me 
the  opportunity  of  making  the  ante-mortem  diagnosis.  The  clinical 
notes  were  made  by  Dr.  C.  R.  Joyce,  house-physician  in  charge,  with 
my  own  collaboration. 

Case.   G.   R.,   Englishman,   aged  thirty-six,   intelligence  above  the 

average,  never  had  chorea,  rheumatism,  or  venereal  disease,  and  had 

never  used  tobacco  or  alcohol.  Admitted  to  the  Royal  Victoria  Hospital, 

Montreal,  on  October  27,  19 14,  immediately  upon  his  arrival  in  Canada 

from  England,  being  referred  by  the  Immigration  authorities  on  account 

of  his  cardiac  condition.  Complained  of  slight  dyspnoea,  weakness,  and 

sense  of  pulsation  in  the  temples.  Gave  a  history  of  having  been  in 

apparently  perfect  health,  and  leading  a  strenuous  life  following  his  trade 

*  Good  examples  of  so-called  "spontaneous"  aneurysms  rupturing  into  the  pulmonic 
circulation  with  life  maintained  for  some  time  are  the  cases  by  Roberts  (20)  and  Gaird- 
ner  (21). 


902  RUPTURED  ANEURYSM 

as  a  carpenter,  and  also  working  as  a  Methodist  preacher,  until  the  age  of 
twenty-seven,  when  he  suddenly  became  aware  of  a  feeling  of  cardiac 
irregularity  and  of  throbbing  in  the  temples.  He  took  to  bed  under  medical 
advice,  and  a  month  later  was  admitted  unimproved  to  the  Grantham 
Hospital,  Surrey,  England,  where  he  remained  in  bed  for  nine  months. 
Here  the  diagnosis  of  aneurysm  was  made  and  the  intense  precordial  vibra- 
tion, which  is  perfectly  evident  to  his  own  senses,  is  stated  by  bim  to  have 
been  first  noted.  After  his  discharge  he  remained  in  bed  at  home  for  fifteen 
months  longer,  when  the  signs  of  cardiac  insufficiency  passed  off,  and  he 
was  able  from  this  time  until  his  sailing  from  England  to  follow  his  work 
as  a  Methodist  preacher  (though  not  his  trade  as  a  carpenter),  without 
subjective  symptoms.  The  precordial  vibration,  however,  bad  persisted  to 
the  present  time.  He  was  extremely  seasick  on  shipboard. 

Examination  showed  a  tall,  spare,  poorly  nourished  man,  of  flabby 
musculature,  dyspnoeic  on  exertion,  without  cyanosis,  clubbing,  or  oedema. 
Posterior  cervical,  sub-maxillary,  and  axillary  glands  slightly  enlarged. 
Marked  pyorrhoea  alveolaris.  Temperature  ioo°,  remittent  type.  Wasser- 
mann  negative,  haemoglobin  65  per  cent,  R.B.C.  3,230,000,  W.B.C.  12,300. 
Pulse  84,  waterhammer.  Marked  pulsation  in  temples  and  vessels  of  neck. 
Capillary  pulse. 

Heart.  Slight  precordial  bulging  and  widely  distributed  heaving 
impulse  over  whole  precordium.  Apex  beat  visible,  precordial  vibration 
and  very  strong  diastolic,  almost  continuous,  thrill,  felt  over  the  precordium, 
of  maximum  intensity  in  second  and  third  left  interspaces,  where  it  is  so 
strong  that  a  vibration  may  be  felt  when  the  fingers  are  held  half  an  inch 
away  from  the  chest.  This  thrill  is  transmitted  to  the  right  nipple  line, 
below  to  the  seventh  rib,  above  to  the  clavicle,  and  to  the  left  to  the 
midaxillary  line.  Slight  presystolic  thrill  at  apex,  and  systolic  thrill  in 
vessels  of  neck.  Heart  dullness  at  second  space,  3^  cm.  to  right  and  15^ 
cm.  to  left  of  midsternal  line.  At  apex  systolic  and  diastolic  murmurs, 
transmitted  to  posterior  axillary  line,  and  a  rough  presystolic  murmur. 
At  the  base  a  very  loud  rough  diastolic  murmur  almost  continuous,  being 
interrupted  for  only  a  brief  time  in  systole  with  maximum  intensity  in  third 
left  interspace.  This  murmur  is  extremely  superficial  and  may  be  heard  with 
the  ear  2  inches  from  the  chest  wall.  Another  rough  systolic  murmur  is  heard 
best  over  pulmonary  cartilage.  To-and-fro  murmurs  behind  from  apex  of 
left  lung  to  level  of  fifth  dorsal  spine. 

During  the  succeeding  months  the  temperature  became  high  and  of 
septic  type  (98"  to  105°),  with  occasional  severe  chills.  Blood  cultures 
on  November  loth  and  December  21st  negative.  Weakness  and  dyspnoea 
became  progressively  worse,  vomiting  set  in,  albuminuria,  hematuria. 


X'T^S  PAS-IVG   :-"RC?'   R.V.    TC 
r?ASE. 


Fig.  2.  View  from  Right  Ventricle  of  the  Case  Seen  in  Fig.  i. 

Showing  Probes  passing  through  (a)  Trumpet-Shaped  Tube,*  in  the  picture.  Fringed 
with  Vegetations  (the  Ruptured  Aneurysm  of  the  Sinus  Valsalva)  Projecting  into  the 
Conus  Arteriosus  Directly  below  the  Junction  of  the  Posterior  and  Left  Anterior  Pul- 
monary Cusps;  and  (6)  the  Communication  lying  also  in  the  Conus  directly  subjacent 
of  the  Septal  Defect  with  the  Left  Ventricle;  (c)  Vegetative  and  Ulcerative  Endocar- 
ditis of  the  Pulmonary  Valves  and  of  the  Mural  Endocardium  Adjacent  and  Opposite 
to  the  Ruptured  Aneurysm;  (d)  Dilatation  of  the  Pulmonary  Artery. 

From  a  drawing  by  Dr.  J.  H.  Atkinson. 


Fig.  3.  Model  of  the  Heart  of  a  Human  Embryo  4.6  mm.  Long  x  108,  to  Show  the 
Relation  of  Embryonic  Bulbus  Cordis  to  Ventricle  and  Aortic  Arches. 

(The  Division  of  the  Bulbus  Cordis  into  Aorta  and  Pulmonary  Artery  beginsa  little  above  the  level 
of  the  Bulbo- Ventricular  Cleft  (B.v.),  and  from  this  point  to  the  level  of  the  Aortic  Semilunar  Cusps  the 
"  Bulbar  "  Septum  Forms  the  Anterior  Part  of  the  Interventricular  Septum  of  the  Heart.)  C,  Carotid  Arch ; 
P.  A.,  Pulmonary  Artery;  Per.,  Pericardium;  Tr.  A.,  Truncus  Arteriosus;  A.  d..  Right  Auricle;  A.  s..  Left 
Auricle:  Au.  c.  Common  Auriculoventricular  Orifice;  B.  v.,  Bulboventricular  Cleft;  V'.,  Common  Ventricle. 
Model  Dy  F.  T.  Lewis  and  M.  E.  Abbott,  (Dr.  Begg's  Embryo). 

{From  the  Anatomical  Laboratory  of  the  Harvard  Medical  School.)  Republished  from  Osier  and 
McCrae's  "System  of  Medicine,"  2nd  Edilton,  1915,  p.  324. 


IkHvl-.B 


Fig.  4.  Left  Half  of  Model  by  Julius  Tandler  of  the  Bulbus  Cordis  of  the 
Embryo  He,  Divided  Longitudinally, 

Showing  Stage  of  Development  in  which  the  Distal  Bulbar  Swellings  i  and  3 
(from  which  the  Aortic  and  Pulmonary  Cusps  Originate)  have  Fused  to  Form  the  Distal 
Bulbar  System,  the  Proximal  Bulbar  Swellings  (p.  Bw.  A.B.)  have  Fused  to  Form 
the  Proximal  Bulbar  Septum,  and  the  Septum  Aortico-pulmonale  {S.a.p.)  has  Grown 
Downward  for  a  Short  Distance,  Leaving  two  Points  01  Communication  between  the 
Aortic  and  Pulmonary  Trunks,  Immediately  above  and  below  the  Distal  Bulbar 
Septum  (Aortic  and  Pulmonary  Cusps).  The  Sound  in  the  Picture  has  Disappeared 
in  the  Lumen  of  the  Pulmonary  Artery  and  Reappears  in  the  Common  Lumen  above 
and  below  the  Distal  Septum  at  these  Two  Points  of  Communication.  These  Points 
thus  Correspond  in  Location  to  the  Openings  above  and  below  the  Right  Aortic  Cusp 
Seen  in  Case  Reported. 

"A..  Aorta  (4th  Aortic  Arch);  D.  Bw,  1-3,  Distal  Bulbar  Swellings;  P.  Attachment  of  Pericardium; 
p.  Bno.  A.  B.,  Proximal  Bulbar  Swellings  A.  B.;  P/.,  Pulmonary  Artery  (Sixth  Aortic  Arch);  S.a.p.,  Septum 
Aorto-pulmonale;*,  point  at  which  the  sound  of  the  Lumen  of  the  Pulmonary  Artery  disappears,  being 
covered  by  the  Fusion  of  the  Distal  Bulbar  Swellings  i  and  3,  forming  the  Distal  Bulbar  Septum;**  point  at 
which  the  sound  again  appears  in  the  Common  Lumen.  The  subdivision  of  the  Common  Efferent  Tube  is 

Produced  distally  by  the  Septum  Aorto-pulmonale,  in  the  middle  region  by  the  Distal  Bulbar  Septum,  and 
'roximally  by  the  Proximal  Bulbar  Septum.  Between  these  three  portions  of  the  partition  there  are  two 
points  of  communication,  in  which  the  ends  of  the  sounds  are  visible." 

From  Keibel  and  Mall's  "Embryology,"  Vol.  II,  Fig.  384,  p.  552. 


Fig.  5.  Heart  of  Alligator  Mississippiensis. 

View  Showing  Right  Chambers,  Pulmonary  Artery  and  Left  Aortic  Arch  (Arising 
Anteriorly  from  Right  Ventricle),  also  Right  Aortic  Arch  (Arising  Posteriorly  from 
Left  Ventricle). 

The  Foramen  Panizzae  lies  behind  the  Posterior  Cusp  of  the  Left  Aorta  (in  right  ventricle),  and 
Communicates  with  the  Right  Aorta  just  behind  its  Anterior  or  Right  Coronary  Cusp  (in  left  ventricle) 
(which  is  the  Location  of  the  "Aneurysm  of  the  Right  Aortic  Sinuses  of  Valsalva  ").  It  is  marked  by  a  white 
rod.  The  Right  Aortic  Arch  is  marked  by  a  dark  rod.  It  slants  obliquely  upward  from  left  to  right  and  gives 
off  in  its  course  the  Carotid  Arch. 

From  a  specimen  in  Professor  Huntington's  Anatomical  Museum,  College  of  Physicians  and  Surgeons,  Columbia 

University,  New  York. 


i 


RUPTURED  ANEURYSM  903 

and  slight  oedema  developed,  but  never  any  cyanosis.  The  patient  died 
March  5,   1915. 

Clinical  Diagnosis.  Aortic  insufficiency.  Congenital  or  acquired  com- 
munication (probably  ruptured  aneurysmal)  between  aorta  and  pulmonary 
artery  or  base  of  right  ventricle.  Malignant  endocarditis,  or  endarteritis, 
about  the  margins  of  the  communication. 

The  autopsy  was  done  by  Professor  Horst  Oertel,  from  whose  report 
the  following  abstract  is  quoted,  with  his  kind  permission. 

Body,  180  cm.  long,  of  indifferent  physique  and  poor  nutrition.  Skin 
pale,  p)etechial  haemorrhages  on  thighs,  oedema  of  legs.  Chest  bulging. 

On  opening  thorax  precordial  area  occupied  largest  part,  goodly  amount 
of  clear  yellow  fluid  in  both  pleural  and  peritoneal  cavities.  Pericardium 
contains  200  c.c.  clear  fluid,  parietal  pericardium  free,  thin,  no  pleuro- 
pericardial  adhesions.  Aortic  and  pulmonary  valves  the  seat  of  an  extensive 
productive  ulcerative  endocarditis  which  leads  to  the  formation  of  massive 
polypoid  vegetations  and  loss  of  substance  on  the  cusps  of  the  valves  and 
on  the  right  side  on  the  parietal  endocardium  adjoining  the  valve.  Two 
perforations  exist,  leading  to  communications  between  left  and  right 
sides  of  heart.  The  first  takes  its  origin  from  the  sinus  of  Valsalva  of  the 
middle  aortic  cusp,  and  forming  an  aneurysmal  pouch  or  trumpet  which 
projects  into  the  right  ventricle  between  the  septal  and  middle  cusps  of 
the  pulmonary,  has  perforated  into  the  right  heart.  The  second  perfora- 
tion exists  immediately  below  this,  and  extends  through  the  septum  of 
the  ventricles  by  an  irregular  ulceration  of  the  musculature,  immediately 
below  septal  cusp  of  the  aorta  to  immediately  below  septal  cusp  of  the 
pulmonary  artery.  A  few  small  verrucose  vegetations  on  mitral.  Tricuspid 
quite  free,  also  auricles.  Marked  hypertrophy  of  both  sides  of  heart. 

Lungs  compressed,  oedematous,  and  contain  multiple  haemorrhagic 
infarcts.  Congestion  of  ileum  and  oedema  and  congestion  of  large  intestine. 
Cyanosis  of  liver.  Spleen  weighed  375  grams,  enlarged,  firm,  dark  red. 
Haemorrhagic  and  productive  nephritis. 

A  detailed  description  of  the  heart,  which  was  handed  over  to 
the  writer  for  further  study,  follows: 

A  heart  greatly  dilated  and  hyp>ertrophied  in  its  left  ventricle  and 
auricle,  and  also,  though  to  a  less  extent,  in  its  right  chambers.  Depth 
of  left  ventricle  from  base  of  anterior  aortic  cusps  to  apex  12  cm.,  thickness 
of  wall  1.6  cm.,  thickness  of  right  ventricle  6  cm.  Pulmonary  artery  and 
orifice  dilated,  circumefrence  at  valves  8.5  cm.  Circumference  of  aorta 
at  same  level  6.5  cm.  Aortic  and  pulmonary  cusps  thickened  and  in- 
sufficient, and  covered  with  recent  vegetations  which  extend  upon  the 


904  RUPTURED  ANEURYSM 

upper  surfaces  of  the  aortic  cusps  and  upon  the  mural  endocardium  of  the 
base  of  both  ventricles,  and  are  especially  redundant  in  the  conus  of  the 
right  ventricle  on  its  anterior  and  septal  walls. 

The  right  anterior'  aortic  sinus  of  Valsalva  presents  in  its  floor,  below 
the  orifice  of  the  right  coronary  artery,  a  large  orifice  admitting  the  finger, 
which  leads  into  a  tubular  trumpet-shaped  process,  2  cm.  long,  which 
projects  into  the  right  ventricle  between  the  septal  and  median  pulmonary 
cusps,  and  represents  a  ruptured  aneurysm  of  the  sinus.  The  walls  of  this 
tubular  canal  are  thick  and  tendinous,  and  are  coyered  externally  in  the 
conus  of  the  right  ventricle  by  polypoid  vegetations,  and  the  free  borders 
of  its  ruptured  orifice  are  fringed  with  vegetations  which  have  impinged 
upon  the  opposite  (anterior)  conus  wall  and  have  evidently  led  by  secondary 
infection  to  the  development  of  a  great  patch  of  vegetations  5  cm.  square, 
which  occupies  this  position.  (See  Plate  II.) 

Directly  below  the  right  anterior  cusp  in  the  left  ventricle  is  seen 
a  second  opening  leading  into  the  conus  of  the  right  ventricle.  It  is  of 
ovoid  shape,  about  i  cm.  long,  and  has  as  its  upper  border  the  base  and 
ventricular  surface  of  the  right  aortic  cusp,  which  on  its  aortic  surface 
is  continuous  with  and  helps  to  form  the  floor  of  the  trumpet-shaped 
aneurysm  of  the  sinus.  The  lower  and  anterior  borders  of  this  inter- 
ventricular opening  on  the  side  of  the  left  ventricle  are  rounded  and 
muscular,  but  this  is  partly  obscured  by  tendinous  thickening  and  by  a 
superimposed  flattened  film  of  vegetations.  (See  Plate  I.)  The  posterior 
border  of  the  defect  lies  i  .5  cm.  anterior  to  the  pars  membranacea,  that 
is.  it  is  not  in  the  situation  usually  occupied  by  interventricular  septal 
defects,  but  lies  in  the  extreme  anterior  or  bulbar  part  of  the  inter- 
ventricular septum  in  the  usual  situation  occupied  by  bulbar  septal  defects. 
Seen  from  the  right  ventricle  this  interventricular  communication  opens 
into  the  conus  immediately  below  and  to  the  left  of  the  ruptured  sinus 
aneurysm.  Its  edges  are  ulcerated  and  destroyed,  and  it  is  surrounded  by 
masses  of  vegetations. 

The  left  anterior  aortic  cusp  is  displaced  downward  5  cm.  below  the 
left  coronary,  and  an  interval  of  i  cm.  exists  between  it  and  the  right 
anterior  cusp.  This  interval  is  filled  with  a  mass  of  vegetations,  and  these 
have  burrowed  freely  into  the  myocardium  adjacent. 

Remarks  upon  this  Case.  Clinical,  i.  As  has  been  said,  the 
diagnosis  of  a  communication  between  the  base  of  the  aorta  and 

*  A  note  upon  the  nomenclature  of  the  aortic  cusps  is  necessary.  Gray,  Morris* 
mention  an  anterior  (right  coronary)  and  two  right  and  left  posterior  (left  coronary) 
cusps.  But  that  used  by  the  older  writers  and  in  the  German  articles  is  right  and  left 
anterior  (right  and  left  coronary)  and  posterior  (free)  cusp,  and  it  is  this  terminology 
that  is  followed  here. 


RUPTURED  ANEURYSM  905 

the  pulmonary  circulation,  which  was  so  obvious  here,  was  based 
on  the  localization  of  maximum  intensity  of  the  continuous  murmur 
and  thrill  over  the  middle  of  the  precordium,  and  the  intensity  and 
extraordinary  proximity  of  these  signs  to  the  chest  wall,  which 
differentiated  it  from  patent  ductus.  The  question  as  to  the  time  the 
communication  occurred,  that  is,  whether  it  had  been  present 
throughout  life  (indicating  a  congenital  perforation)  or  had  existed 
for  some  years  (pointing  to  a  ruptured  aneurysm),  or  was  syn- 
chronous only  with  the  present  attack  of  malignant  endocarditis, 
and  due  possibly  to  its  ravages,  was  of  equally  great  interest.  In 
view  of  the  intelligence  of  the  patient,  his  emphatic  assurance  that  the 
precordial  vibration,  which  was  perfectly  evident  to  his  sight  and 
touch,  had  appeared  at  the  time  of  his  first  cardiac  breakdown, 
nine  years  ago,  and  had  persisted  since,  was  important.  Since, 
however,  the  diagnosis  of  an  aneurysm  rupturing  at  this  time 
depended  on  the  accuracy  of  this  statement,  it  was  important  to 
confirm  it.  Through  the  kindness  of  Professor  Arthur  Keith,  London, 
the  following  facts  were  obtained  from  the  Grantham  Hospital, 
England.  The  patient  was  sent  in  by  Dr.  G.  M.  Shipman,  and  the 
entry  relating  to  him  in  the  hospital  case-book  read:  "G.  R.,  aged 
twenty-seven,  admitted  August  14,  1905.  Discharged  May  3,  1906. 
Disease,  aneurysm  of  the  aorta.  Result,  in  statu  quo."  Dr.  Shipman 
further  wrote  Dr.  Keith  "Re  G.  R.,"  that  he  "remembered  the  case 
of  aneurysm  of  the  aorta  perfectly,  and  would  look  up  some  notes 
which  he  had  about  him."  Owing  to  the  war  exigencies  these  notes 
have  not  yet  been  received,  but  the  above  information  is  sufficiently 
confirmatory  of  the  patient's  statements  to  make  the  diagnosis  of 
aneurysm  of  the  base  of  the  aorta  rupturing  into  the  pulmonary 
circulation  nine  years  before  death  a  practical  certainty. 

2.  The  marked  diastolic  character  of  the  almost  continuous 
murmur  was  of  interest.  This  was  present  also  in  several  of  the 
cases,  but  is  not  a  constant  feature,  and  may  have  had  to  do  with 
the  rough  vegetations  at  the  orifice  of  the  trumpet-shaped  tube 
through  which  the  blood  passed  in  diastole.  The  complexity  of  the 
other  murmurs  present  is  readily  explained  by  the  aortic  and 
pulmonary  insufficiency  that  existed,  and  the  masses  of  vegetations 
that  blocked  the  pulmonary  conus. 

3.  The  marked  dyspnoea,  without  cyanosis,  was  confirmatory 


9o6  RUPTURED  ANEURYSM 

evidence  that  the  course  of  the  blood  through  the  ruptured  aneurysm 
and  ventricular  communication  was  from  the  left  to  the  right  heart, 
owing  to  the  fact  that  the  pressure  is  physiologically  highest  in  the 
left  (systemic)  ventricle.  In  such  cases  the  volume  of  blood  in  the 
pulmonary  circulation  is  necessarily  increased.  An  effort  was  made 
to  obtain  confirmation  of  this  by  determining  the  basal  carrying 
tension  of  the  alveolar  air  for  oxygen  according  to  the  method 
suggested  by  Plesch,  (i6)  but  no  results  were  obtained  owing  to 
inadequacy  of  apparatus. 

4.  The  youth  of  the  patient  at  the  first  onset  of  symptoms, 
together  with  the  complete  absence  of  luetic  history,  suggested 
a  traumatic  or  congenital  origin  of  the  ruptured  aneurysm.  He  gave 
a  history  of  striking  his  chest  violently  over  the  precordium  against 
a  pointed  instrument  (semaphore)  at  the  age  of  four,  and  this 
trauma  was  insisted  upon  as  a  cause  by  himself  and  by  his  father, 
who  wrote  us  several  letters.  The  idea  was  discarded  by  me  as  im- 
probable, in  favour  of  a  probably  congenital  origin  with  rupture 
as  a  result  of  strain. 

5.  The  septic  temperature  and  chills,  which  grew  progressively 
worse,  pointed  definitely  to  an  acute  infective  process  which  was 
believed  by  me  to  be  secondary  to  the  ruptured  aneurysm. 

Pathological  Anatomy.  The  pathological  interest  of  this  specimen 
lies  in:  (i)  the  ruptured  aneurysm  of  the  right  aortic  sinus  of  Val- 
salva; (2)  the  interventricular  communication  directly  below  the 
same  aortic  cusp;  (3)  the  marked  thickening  of  aortic  and  pulmonary 
valves  and  evidences  in  the  great  size  and  thickness  of  the  left 
ventricle  of  an  aortic  insufficiency  of  long  standing;  (4)  the  extrav- 
agant vegetations  of  malignant  endocarditis,  which  cover  the 
aortic  and  pulmonary  cusps,  surround  the  margins  of  the  inter- 
ventricular communication,  especially  in  the  right  ventricle,  fringe 
the  borders  of  the  ruptured  aneurysm,  and  cover  the  opposite  wall 
of  the  right  ventricle. 

The  presence  of  such  an  extensive  acute  infective  endocarditis, 
together  with  the  evidences  of  an  old  inflammatory  process,  obscures 
the  nature  of  the  two  openings  into  the  right  ventricle  somewhat, 
and  led  to  a  difi'erence  of  opinion  at  the  autopsy  as  to  their  nature — 
their  irregular  ulcerated  outline,  especially  on  the  side  of  the  right 
ventricle,  and  their  encrustment  with   vegetations   suggesting  a 


RUPTURED  ANEURYSM  907 

possible  inflammatory  origin.  The  clinical  history  of  the  case, 
however,  pointing  to  a  ruptured  aneurysm  of  nine  years*  standing; 
the  finger-like  character  and  position  of  this  aneursym,  identical 
in  all  respects  with  the  cases  reported,  in  which  an  exactly  similar 
tube  with  thin  membranous  walls  and  without  any  sign  of  in- 
flammation projected  into  the  right  ventricle  in  an  exactly  similar 
situation;  the  location  of  the  ventricular  communication  directly 
below  the  same  aortic  cusp  and  having  this  cusp  as  its  upper 
border;  its  situation  in  the  anterior  upper  part  of  the  ventricular 
septum  and  opening  into  the  conus  of  the  right  ventricle  in  the  typi- 
cal situation  for  bulbar  septal  defects  (cases  reported  by  Tate,  (17) 
Coupland,  (18)  RoIIeston  (19));  its  shape  and  character  as  seen  from 
the  left  ventricle,  where  the  ravages  of  the  malignant  endocarditis 
are  less  serious;  above  all,  the  combination  of  these  two  conditions, 
namely,  aneurysm  immediately  above  and  ventricular  communica- 
tion immediately  below  the  right  aortic  valve,  as  occurred  in  the 
other  cases  recorded  in  which  there  was  no  sign  of  inflammation  and 
in  which  a  congenital  origin  was  concluded,  led  the  writer  to  conclude 
that  both  openings  are  here  of  congenital  origin,  due  to  a  thinning 
above  and  a  defect  below  of  the  bulbar  septum  between  the  two 
great  trunks  which,  in  the  submergence  of  the  embryonic  bulbus 
cordis,  forms  the  extreme  upper  and  anterior  part  of  the  inter- 
ventricular septum,  the  congenitally  thin  wall  of  the  right  aortic 
sinus  yielding  under  the  pressure  of  the  circulation  and  forming 
the  trumpet-shaped  pouch  which  projected  into  the  right  ventricle 
and  ruptured  as  a  result  of  strain.  The  great  redundancy  of  the 
vegetations  in  the  pulmonary  conus  supports  the  view  of  their 
secondary  origin  about  the  defects,  for  it  is  not  usual  for  endocarditis 
to  develop  in  this  situation  without  determining  cause. 

Development.  A  study  of  the  development  of  the  aortic  and 
anterior  part  of  the  interventricular  septum  gives  striking  con- 
firmation to  the  view  that  both  sinus  aneurysm  and  septal  com- 
munication are  due  to  a  defective  development  of  the  embryonic 
bulbar  septum.  As  is  well  known,  in  the  earlier  stages  of  the  embry- 
onic heart,  the  arterial  trunk  or  eff'erent  tube  consists  of  the  muscular 
bulbus  cordis  of  the  ventricle,  which  gives  ofi"  the  embryonic  aortic 
arches  from  its  upper  border  (see  Plate  III),  and  is  lined  by  endo- 
cardial swellings  spirally  arranged  (which  persist  in  some  of  the 


9o8  RUPTURED  ANEURYSM 

fishes  as  rows  of  valves).  As  division  of  the  heart  proceeds  by 
development  of  its  septa  the  division  of  the  primitive  arterial  trunk 
takes  place  in  the  part  derived  from  the  bulbus  cordis  by  fusion  of 
the  "proximal"  and  "distal"  pairs  of  bulbar  swellings,  and  at  the 
extreme  distal  end  by  a  septum  growing  down  from  above  between 
the  aorta  and  the  pulmonary  artery.  The  distal  bulbar  swellings 
correspond  to  the  site  of  the  future  aortic  cusps.  There  thus  exists 
a  stage  in  the  development  of  the  aortic  septum  in  which  the 
septum  aortico-pulmonale  is  growing  downward  from  above,  the 
distal  bulbar  swellings  have  united  in  the  middle  and  the  proximal 
bulbar  swellings  are  united  below,  leaving  two  apertures  where  the 
arterial  trunk  is  still  common  immediately  below  and  above  the 
future  aortic  and  pulmonary  cusps.  This  stage  of  development  has 
been  reconstructed  by  Julius  Tandler  and  is  figured  in  Keibel  and 
Mall's  "Embryology,"  2d  edition,  Fig.  384,  and  the  plate  is 
reproduced  in  this  article.  The  probe  passes  from  the  lumen  of  the 
pulmonary  artery  through  two  apertures  which  occupy  the  exact 
location  of  the  defects  seen  in  the  cases  of  aneurysm  of  the 
right  aortic  sinus  of  Valsalva  and  the  anterior  interventricular 
septal  defects  in  the  cases  described  by  Hale-White,  Thurnam, 
Kraus,  Hart,  and  in  the  specimen  which  forms  the  subject  of 
this  paper. 

Comparative  Anatomy.  A  study  of  the  hearts  of  reptiles  and 
amphibians,  made  for  confirmatory  purposes  in  Professor  Hunting- 
ton's Collection  at  Columbia  University,  New  York,  elicited  the 
extremely  interesting  information  that  this  aperture  above  the 
anterior  aortic  cusp  of  the  right  aorta  in  the  crocodile  remains 
permanently  open  and  allows  the  aerated  blood  from  the  right  aortic 
arch  (which  arises  from  the  left  ventricle  and  supplies  the  systemic 
circulation),  to  pass  into  the  left  aortic  arch  (which  arises  from  the 
right  ventricle  and  receives  unaerated  blood)  through  an  aperture 
above  its  posterior  cusp.  This  is  the  so-called  foramen  Panizzae  of 
the  crocodile  (see  Plate  V),  and  the  aneurysm  of  the  right  aortic 
sinus  would  seem  to  represent  a  persistence  of  the  same  opening. 
It  was  seen  in  the  human  subject  not  as  an  aneurysm,  but  as 
a  complete  defect  in  the  cases  reported  by  Rickards  and  Charteris. 
This  view  is  confirmed  by  a  perusal  of  the  comprehensive  studies 
by  Langer  (22)  and  Greil  (23)  upon  the  developmental  changes  in 


RUPTURED  ANEURYSM  909 

the  reptilian  bulbus  cordis  in  successive  stages,  which  gives  inter- 
esting confirmation,  from  the  field  of  comparative  embryology,  of 
Tandler's  reconstruction. 

Summary  oj  Literature.  For  purposes  of  comparison  the  cases 
in  the  literature  of  congenital  communications,  or  aneurysm,  of  the 
right  aortic  sinus  of  Valsalva  into  the  right  ventricle,  are  herewith 
briefly  summarized. 

I.  Thurnam  (7)  (1840).  "Ruptured  Aneurysm  of  Right  Aortic  Sinus  of 

Valsalva.  Malignant  Endocarditis."  Aneurysm  projecting  into  and 
communicating  by  two  rounded  openings  with  base  of  right  ventricle; 
recent  endocarditis;  pulmonary,  aortic,  and  mitral  insufficiency;  hy- 
pertrophy and  dilatation  of  heart. 

Male,  aged  thirty-three.  Rheumatism  at  twenty.  Sudden  onset 
while  in  perfect  health,  with  sense  of  "cracking"  in  heart  region,  of 
faintness,  palpitation,  dyspnoea,  haemoptysis,  anasarca,  extraordinarily 
superficial  continuous  sawing  murmur  with  tremor  intense  in  left 
second  interspace.  Death  eleven  weeks  later. 

II.  Beck  (2)  (1842).  "Ruptured  Aneurysm  with  Interventricular  Com- 
munication." Right  aortic  valve  calcified,  sinus  enlarged,  presenting 
round  opening  leading  into  collapsed  sac-like  glove-finger  three- 
quarters  inch  long,  projecting  into  right  ventricle  between  healthy 
pulmonary  valves.  Three  rounded  openings  in  tip  and  sides.  Below 
it,  interventricular  communication  admitting  goose-quill,  believed 
by  author  to  be  congenital. 

Male,  aged  thirty-one.  Palpitation  on  exertion  always.  Signs  of 
cardiac  insufficiency  and  marked  dyspnoea  three  years,  anasarca 
developed.  Very  superficial  sawing  murmur  with  tremor,  loudest  in 
diastole  but  continuous,  with  maximum  intensity  at  base  of  heart. 

III.  Rickards  (i)  (1881).  "Congenital  Communication  in  Right  Aortic 
Sinus  with  Right  Ventricle.  Septal  defect."  Right  and  left  anterior 
aortic  valves  congenitally  fused,  behind  right  half  large  round  orifice 
with  smooth  membranous  funnel-shaped  walls  opening  into  right  ven- 
tricle between  healthy  pulmonary  cusps.  Immediately  below  same 
cusp  circular  aperture  in  septum  with  smooth  membranous  walls 
passing  into  conus  of  right  ventricle.  Both  openings  considered  by 
author  congenital. 

Male,  aged  thirty.  Precordial  discomfort  and  dyspnoea  always. 
Loud,  rough,  double  murmur  practically  continuous,  systolic  element 
loudest,  maximum  between  third  cartilages,  intense  purring  double 
precordial  vibration.  Epistaxis,  haemoptysis. 


910  RUPTURED  ANEURYSM 

IV.  Charteris  (15)  (1883).  "Congenital  Communication  in  Right  Aortic 
Sinus  with  Right  Ventricle."  Immediately  behind  right  aortic  valve 
rounded  opening  with  firm  margins  leading  into  right  ventricle. 
Patch  of  endocardial  thickening  on  opposite  wall  of  right  ventricle. 

Male,  aged  fifty-three.  Died  from  cardiac  insufficiency.  Systolic 
murmur  most  distinct  at  apex. 

V.  Krzywicki  (4)  (1889).  "Ruptured  Aneurysm  of  Right  Aortic  Sinus." 
In  sinus  oval  opening  with  tendinous  borders  leading  into  thimble- 
shaped  cavity  2.5  cm.  deep,  extending  into  right  ventricle  with  thin, 
almost  transparent,  membranous  covering  formed  of  very  delicate 
connective  tissue  with  endocardial  covering  derived  from  right  ven- 
tricle. Bean-shaped  perforation  at  apex. 

Female,  aged  twenty.  Nine  months  before  death  pleurisy,  precordial 
pain,  palpitation,  anasarca.  Systolic  murmur  over  base. 

VI.  Hale-White  (3)  (1891).  "Ruptured  Aneurysm  of  Right  Aortic  Sinus 
with  Septal  Defect."  Septum  deficient  just  below  right  aortic  valve, 
ovoid  opening  margins  thickened,  septum  for  three-quarters  inch 
around  thin,  semitransparent.  Sinus  above  valve,  thin-walled  pouch 
which  bulged  three-quarters  inch  into  right  ventricle  with  ap>erture  at 
bottom.  Two  patches  of  endocardial  thickening  on  wall  of  right  ventricle 
opposite  defects. 

Male,  aged  fifteen.  Symptoms  four  months,  dyspnoea,  oedema, 
precordial  vibration,  rasping  to-and-fro  murmurs  simulating  pericardial 
friction,  maximum  at  third  interspace. 

VII.  Kraus  (5)  (1902).  "Ruptured  Aneurysm  of  Right  Aortic  Sinus.  Inter- 
ventricular Communication.  Old  Endocarditis."  Wall  of  right  aortic 
sinus  thinned  and  membranous,  pushed  into  right  ventricle  just  below 
pulmonary  valves  as  sac  2.5  cm.  long,  carrying  on  anterior  surface 
diverticulum  with  delicate  walls,  perforated  at  apex.  Walls  of  sac 
smooth  and  glistening.  Semilunar  opening  in  septum  just  below  right 
aortic  cusp.  Endocardium  surrounding  this  extensively  scarred. 

Male,  aged  twenty-seven.  Symptoms  four  years,  onset  after  severe 
muscular  strain.  Dyspnoea,  palpitation,  cyanosis,  anasarca,  haemop- 
tysis. Marked  systolic  thrill  and  coarse,  long  systolic  murmur  almost 
continuous,  with  short,  hissing,  roaring  diastolic  element,  maximum  at 
second  and  third  interspaces. 

VIII.  Hart  (6)  (1905)  (Case  III).  "Ruptured  Aneurysm  of  Right  Aortic 
Sinus.  Septal  Defect.  Malignant  Endocarditis."  Semilunar  opening 
in  septum  just  below  right  aortic  cusp,  opening  in  conus  of  right 
ventricle.  Just  above  it,  sacculation,  size  of  walnut,  of  right  aortic 
sinus  with  extremely  transparent  membranous  wall  reaching  forward 


r 


RUPTURED  ANEURYSM  911 

into  pulmonary  conus  in  semicircular  form  just  between  right  pul- 
monary cusps.  Fibrous  ring  below  aortic  valves.  Malignant  endocarditis 
of  margins  of  septal  defect,  left  pulmonary  cusp,  and  fibrous  ring, 
considered  by  author  secondary  to  septal  defect  and  sinus  aneurysm 
of  congenital  origin. 
IX.  Author's  Case  (1919).  "Ruptured  Aneurysm  of  Right  Aortic  Sinus. 
Interventricular  Communication  (believed  to  be  Bulbar  Septal  Defect). 
Malignant  Endocarditis." 

Male,  aged  thirty-six.  Onset  of  symptoms  nine  years  before  death 
with  dyspnoea,  precordial  vibration  and  sawing,  continuous  murmur 
with  diastolic  accentuation.  Cardiac  efficiency  re-established  after 
two  years*  illness,  but  physical  signs  persisted.  Second  cardiac  break- 
down with  malignant  endocarditis  nine  months  before  death. 

Conclusions 

1.  A  case  is  reported  of  aneurysm  of  the  right  aortic  sinus  of 
Valsalva  rupturing  into  the  right  ventricle  associated  with  inter- 
ventricular communication  and  malignant  endocarditis. 

2.  The  presence  of  the  characteristic  physical  signs  of  com- 
munication between  the  base  of  the  aorta  and  the  pulmonary 
circulation,  namely,  coarse  precordial  vibration  and  continuous 
sawing  murmur  with  diastolic  accentuation  superficially  placed, 
and  with  maximum  intensity  over  the  second  and  third  interspaces, 
justified  this  diagnosis,  which  was  made  during  life. 

3.  The  clinical  evidence  accumulated  was  sufficient,  in  the 
judgment  of  the  writer,  to  warrant  the  conclusion  that  the  aneurysm 
ruptured  into  the  right  ventricle  nine  years  before  death.  During 
this  time  the  patient  maintained  a  moderate  degree  of  cardiac 
efficiency,  showing  that  communication  between  the  two  circula- 
tions is  compatible  with  life  for  a  long  time. 

4.  The  aneurysm  of  the  right  aortic  sinus  and  the  interven- 
tricular communication  are  believed  by  the  writer — on  the  ground 
of  their  location  immediately  above  and  below  the  right  aortic  cusp, 
the  shape  and  appearance  of  the  septal  opening  seen  from  the  left 
ventricle,  the  evidence  of  identical  cases  in  the  literature  unassociated 
with  malignant  endocarditis,  and  the  facts  of  development  and  com- 
parative anatomy, — to  be  of  congenital  origin,  and  due  to  defective 
development  of  the  bulbar  septum  between  the  aortic  and  pulmo- 


912  RUPTURED  ANEURYSM 

nary  trunks  which  forms  the  upper  anterior  part  of  the  ventricular 
septum  in  the  submergence  of  the  bulbus  cordis. 

5.  There  is  a  stage  in  the  development  of  the  aortic  septum  at 
which  two  such  apertures  exist  above  and  below  the  "distal  bulbar 
septum"  which  is  the  site  of  the  aortic  and  pulmonary  valves.  The 
upper  of  these  apertures  remains  permanently  open  in  the  crocodile 
as  the  foramen  Panizzae,  which  is  thus  the  homologue  of  the  aneu- 
rysmal thinning  or  congenital  opening  which  occurs  in  the  right 
aortic  sinus  of  Valsalva. 

6.  The  malignant  endocarditis,  which  is  so  extensive  in  this 
case  as  to  obscure  the  two  openings  in  the  side  of  the  right  ventricle, 
is  believed  by  us  to  be  secondary  to  the  two  defects.  The  extrav- 
agance of  the  vegetations  in  the  conus  of  the  right  ventricle  sup- 
jxjrts  this  assumption,  for  such  processes  rarely  develop  in  this  situa- 
tion without  a  determining  cause. 

In  conclusion,  the  writer's  sincere  thanks  are  due  to  Professor 
W.  F.  Hamilton  for  the  privilege  of  studying  this  remarkable  case 
during  life,  to  Professor  Horst  Oertel  for  placing  the  heart  at  her 
disposal,  to  Dr.  Arthur  Keith  for  the  valuable  information  obtained 
through  his  kindness  from  the  Grantham  Hospital,  to  Professor 
G.  S.  Huntington  for  the  privilege  of  studying  his  admirable  em- 
bryological  and  anatomical  Museum  Collections,  and  for  his  kindness 
in  giving  this  case  his  consideration  and  confirming  the  explanation 
here  given  of  the  developmental  origin  of  the  two  defects,  and  to  Sir 
William  Osier  for  inspiration  and  encouragement  in  the  study  of 
congenital  hearts. 

BIBLIOGRAPHY 

1.  Beck,  "Aneurysm  of  Ascending  Aorta  Bursting  into  Right  Ventricle 

with  a  Communication  between  the  Two  Ventricles, "  Medico-Cbir. 
Tr.,  1842,  XXV,  15. 

2.  Hale- White,   "A  Case  of  Patent  Ventricular  Septum,  together  with 

an  Aneurysm  of  the  Base  of  the  Aorta  Opening  into  the  Right  Ven- 
tricle," Tr.  Path.  Soc.,  Lond.,  1891-92,  XLIII,  34. 

3.  Krzywicki,  "Aneurysms  of  the  Right  Aortic  Sinus  of  Valsalva,"  Zieg. 

Berfr.,  1889,  VI,  473. 

4.  Kraus,  "True  Aneurysm  of  the  Right  Aortic  Sinus  of  Valsalva," 

Berl  klin.  Wcbnscbr.,  1902,  XXIX,  1161. 


RUPTURED  ANEURYSM  913 

5.  Hart,  "Aneurysm  of  the  Right  Sinus  of  Valsalva  of  the  Aorta  and  its 

Relation  to  the  Upper  Ventricular  Septum,"  Vircb.  Arcb.  f.  path. 
Anat.,  1905,  CLXXXII,  167. 

6.  Thurnam,  "Aneurysms,  and  Especially  Spontaneous  Varicose  Aneu- 

rysms of  the  Ascending  Aorta,  and  Sinuses  of  Valsalva."  Case  VII. 
"Spontaneous  Varicose  Aneurysm  of  the  Right  Aortic  Sinus  and 
Summit  of  the  Right  Ventricle  of  the  Heart,"  Medico-Cbir.  Trans. ^ 

1840,  XXIII,  337. 

7.  Peacock,  "Aneurysm  of  the  Ascending  Aorta,  Pressing  upon  the  Base 

of  the  Right  Ventricle  and  Opening  into  the  Origin  of  the  Pulmonary 
Artery;  with  Remarks  on  the  Communication  of  the  Sacs  of  An- 
eurysms with  the  Cardiac  Cavities  and  Adjacent  Vessels,"  Tr.  Patb. 
Soc.  Lond.,  1868,  XIX,  in. 

8.  Brocq,  "  Etude  sur  les  Communications  entre  I'Aorte  et  I'Art^re  Pul- 

monaire  autres  que  celles  qui  resultent  de  la  persistance  du  Canal 
Arteriel,"  Rev.  de  med.,  1885,  V,  1046,  and  1886,  VI,  p.  786. 

9.  Rickards,  "Six  Cardiac  and  Vascular  Cases.  Case  II.  Communica- 

tions between  the  Aorta  and  Pulmonary  and  between  the  Right  and 
Left  Ventricle;  Two  Aortic  Segments,"  Brit.  M.  J.,  1881,  II,  71. 
ID.  Wilkes,  "Communication  between  the  Pulmonary  Artery  and  Aorta," 
Trans.  Patb.  Soc.,  Lond.,  i860,  XI,  57. 

11.  Baginsky,  "Communication  between  Aorta  and  Pulmonary  Artery," 

Berl.  klin.  Wcbnscbr.,  1879,  XLIII,  420. 

12.  Frantzel,  "A  Case  of  Abnormal  Communication  of  Aorta  with  Pul- 

monary Artery,"  Vircb.  Arcb.,  1868,  XLIII,  420. 

13.  Girard,  "  Case  of  Congenital  Communication  between  Aorta  and  Pul- 

monary Artery,"  Zurich  Thesis,  1895. 

14.  Hektoen,  "Rare  Congenital  Anomalies.  Case  I.  Large  Defect  in  Sep- 

tum between  Pulmonary  Artery  and  Aorta,  the  Heart  normally  De- 
veloped. General  Infection  with  Bacillus  Mucosus  Capsulatus," 
Tr.  Patb.  Soc.  Cbicago,  November  12,  1900. 

15.  Charteris,    "Notes  on  a  Case  of  Congenital   Malformation   of  the 

Heart,  Opening  between  Aortic  Valves  and  Right  Ventricle,  Med. 
Press,  er  Cir.,  1883,  XXXV,  354. 

16.  Plesch,  "Zur  Diagnose  der  kongenitalen  Vitien,"  Berl.  klin.  Wcbnscbr., 

1909,  XLVI,  390. 

17.  Tate,  "Case  of  Malformation  of  the  Heart  with  Perforation  of  Ven- 

tricular Septum,"  Tr.  Patb.  Soc.  Lond.,  1892,  XIII,  36. 

18.  Coupland,  "Defect  in  the  Ventricular  Septum  of  the  Heart,  Probably 

Congenital;  unusual  Site  of  Aperture,"  Tr.  Patb.  Soc.  Land.,  1879, 
XXX,  266. 


914  RUPTURED  ANEURYSM 

19.  RoIIeston,  "Communication  between  the  Ventricles  of  the  Heart,"  Tr. 

Path.  Soc.  Lond.,  1891,  XLII,  65. 

20.  Roberts,  "Aneurysm  of  Root  of  Aorta  Communicating  with  Pul- 

monary Artery,"  Brit.  M.  J.,  May  2,  1868,  No.  383. 

21.  Gairdner,  "Aneurysm  of  First  Part  of  Artery  Opening  into  Pulmo- 

nary Artery  and  Conus  Arteriosus  of  Right  Ventricle,"  Glasg.  Hosp. 

Rep.,  1899,  I. 
•  22.  Langer,  "On  the  Development  of  the  Bulbus  Cordis  in  Amphibia  and 

Reptiles,"  Morpb.  Jabrh.,  XXI,  1894. 
23.  Greil,  "Contributions  to  the  Anatomy  and  Development  of  the  Heart 

and  Truncus  Arteriosus  in  Vertebrates,"  Morpb.  Jabrb.,  XXXI, 

1903. 


DETECTION  OF  ABNORMAL  TISSUES  WITHIN 
THE  LUNGS 

By  C.  R.  Bardeen,  M.D.,  University  of  Wisconsin 

ONE  of  my  most  vivid  memories  of  the  teacher  to  whom 
this  volume  is  dedicated  is  the  way  in  which  he  introduced 
to  the  subject  of  physical  diagnosis  the  group  of  medical 
students  to  which  I  belonged.  He  traced  the  early  history  of 
palpation,  auscultation,  and  percussion,  and  pointed  out  the  in- 
difference with  which  these  methods  were  first  met,  and  then  the 
difficulties  which  they  long  suffered,  and  which  they  too  often  still 
suffer  from  lack  of  careful,  objective,  discriminating  study.  He 
emphasized  above  all  the  need  of  co-ordinating  study  of  physical 
diagnosis  with  that  of  normal  and  morbid  anatomy. 

Since  my  student  days  there  has  arisen  an  important  addition 
to  the  time-honored  methods  of  physical  diagnosis,  that  of  roent- 
genology. A  great  addition  has  thus  been  made,  especially  to  methods 
of  physical  examination  of  the  thoracic  cavity.  But,  like  the  older 
methods,  this  new  method  is  either  too  frequently  treated  with 
indifference  or  fails  to  receive  the  accurate  objective  study,  coupled 
with  studies  of  morbid  and  pathological  anatomy  and  experimental 
work  on  animals,  necessary  for  fruitful  yield. 

Thus,  for  instance,  in  the  study  of  the  heart,  the  roentgen  rays 
offer  us  a  far  more  accurate  method  of  determining  its  size  and  some 
features  of  its  activity  than  any  we  have  hitherto  had.  Yet  the 
majority  of  the  relatively  few  who  as  yet  make  use  of  the  roentgen 
rays  in  the  clinical  diagnosis  of  cardiac  conditions  do  no  more  than 
measure  the  transverse  diameter  of  the  heart  silhouette,  and  gain 
Httle  more  information  than  may  be  gained  by  expert  percussion. 

So,  also,  in  the  study  of  the  lungs,  very  few  have  carefully  cor- 
related roentgenological  study  of  the  lungs  with  the  study  of  normal 
and  morbid  anatomy,  as  H.  K.  Dunham  has  done  in  co-operation 
with  W.  S.  Miller. 

The  extent  of  the  possibility  of  distinguishing  within  the  lungs 

915 


9i6       ABNORMAL  TISSUES  WITHIN  THE  LUNGS 

relatively  minute  tissue  alterations  is  appreciated  by  few,  even  of 
the  expert  roentgenologists.  Thus  in  the  first  edition  of  the  rules 
for  medical  examination  under  the  Selective  Service  Act  the  state- 
ment is  made  that  "Tubercle  caseations  as  such  cast  no  shadows 
distinguishable  from  the  other  tissues  of  the  parenchyma."  That 
"it  has  been  found  that  cubes  i  c.c.  in  size  of  caseous  tubercle,  when 
embedded  in  a  healthy  lung,  are  indistinguishable  by  the  x-ray." 
Just  how  the  experiment  was  conducted  is  not  stated,  but  when  I 
read  this  statement  it  struck  me  as  improbable  that  it  could  be  true. 
I,  therefore,  devised  the  experiments  described  below  and  had  them 
carried  out  by  two  of  my  student  assistants,  Mr.  H.  K.  Kasten  and 
Mr.  Louis  Hanson,  who  embodied  their  work  in  a  thesis  for  the 
B.  S.  degree.  This  thesis,  illustrated  by  numerous  photographs,  is 
now  deposited  in  the  library  at  the  University  of  Wisconsin.  Valu- 
able aid  in  the  work  was  contributed  by  Dr.  Howard  Curl,  roent- 
genologist at  the  University  of  Wisconsin. 

For  the  work  large  dogs  were  selected,  several  of  them  with  an 
anteroposterior  chest  diameter  larger  than  that  of  the  average 
man.  The  dogs  were  killed,  one  or  more  small  openings  were  made  in 
the  intercostal  spaces  at  the  side,  opposite  the  lines  of  separation 
between  the  lobes  of  the  lung,  small  pieces  of  tissues  were  inserted 
between  two  lobes,  and  the  lungs  were  inflated.  Pieces  of  tissue 
were  thus  embedded  in  the  midst  of  lung  tissue  without  injury  to 
the  lungs.  The  lungs,  after  inflation,  were  studied  fluoroscopically  and 
then  stereoscopic  pictures  were  taken.  In  some  cases  small  pieces 
of  metal  were  inserted  as  markers.  In  other  cases,  in  order  to  elimi- 
nate the  possibility  of  the  action  of  secondary  rays,  no  such  markers 
were  used.  The  experiment  was  varied  by  tying  the  urinary  bladder 
of  a  small  rabbit  on  the  end  of  a  small  glass  and  inserting  this  be- 
tween two  of  the  lobes.  It  was  then  possible  to  introduce  water  or 
other  fluids  into  this  bladder  and  determine  the  quantity  necessary 
to  make  the  bladder  visible  fluoroscopically  or  in  the  roentgenogram. 

The  most  surprising  result  of  these  experiments  was  that  minute 
pieces  of  tissue,  which  when  embedded  in  the  skin  or  muscles  of  the 
body  wall  are  invisible,  stand  out  clearly  when  in  the  lung  tissue, 
although  they  should  obstruct  the  passage  of  the  rays  as  little  in 
the  one  case  as  the  other.  This  was  true  even  with  the  fluoroscope, 
and  was  strikingly  so  with  stereoscopic  photographs. 


ABNORMAL  TISSUES  WITHIN  THE  LUNGS       917 

As  a  routine,  blocks  of  fresh  animal  tissue  were  cut  as  nearly 
cubical  as  possible.  Some  spherical  pieces  were  also  used.  The  pieces 
varied  in  size  from  a  diameter  of  yi  to  that  of  i  cm.  Of  the  tissues 
studied  cartilage  was  the  most  opaque.  A  piece  a  few  millimeters 
in  diameter  could  be  distinguished  within  the  lung  even  in  animals 
in  which  the  cartilaginous  ribs  could  not  be  distinguished  roent- 
genologically.  The  relative  opacity  of  cartilage  is  important  to  bear 
in  mind,  since  the  bronchial  cartilages,  especially  when  perpendicular 
to  the  rays,  may  lead  one  to  think  of  tubercles.  Of  the  other  tissues 
tried,  liver,  kidney,  spleen,  and  muscle  tissue  seemed  to  be  about 
equally  opaque  to  the  rays.  In  the  rabbit-bladder  experiment  in  a 
large  dog  about  .5  c.c.  of  water  was  sufficient  to  give  a  visible  shadow. 

From  these  experiments  we  may,  therefore,  conclude  that  it  is 
possible  to  distinguish  by  means  of  the  roentgen  rays  much  more 
minute  alteration  in  the  tissues  than  many  observers  have  as  yet 
been  willing  to  acknowledge,  and  that  the  limits  of  diagnosis  of 
pulmonary  lesion  by  means  of  the  roentgen  rays  are  far  from 
reached.  What  is  needed  is  a  careful  correlation  between  roent- 
genology and  normal  and  pathological  anatomy. 


:s 


) 


THE   CONDITIONS    PRESENTED    IN   THE    HEART 
AND  KIDNEYS  OF  OLD  PEOPLE 

By  W.  T.  Councilman,  M.D.,  Boston,  Mass. 

OLD  age  is  to  be  regarded  as  a  part  of  the  evolution  of  the 
body;  it  is  not  a  pathological  condition  produced  by  the 
agency  of  causes  external  to  the  organism,  but  the  source  of 
the  essential  changes  in  the  tissues  which  constitute  the  condition  is 
inherent  in  the  germ.  The  phenomena  which  are  exhibited  by  the 
aged  individual,  differing  as  they  do  from  the  phenomena  of  earlier 
life,  are  due  to  changes  which  have  gradually  taken  place  in  the 
material  of  the  body.  It  is  impossible  to  comprehend  age  without 
recognizing  that  we  have  to  do  with  a  body  differently  constituted 
from  that  of  earlier  life.  Some  of  the  changes  have  begun  early, 
others  are  late  in  appearance,  some  are  easily  recognized,  and  certain 
of  the  changes,  non-recognizable  by  present  methods,  must  be 
assumed  from  the  differences  in  the  reaction  of  the  material.  The 
mode  of  development,  the  character  of  these  changes,  and  the 
reactions  of  the  body  so  altered  constitute  the  anatomy  and  physi- 
ology of  old  age,  about  which  we  know  very  much  less  than  we  know 
of  the  body  and  its  reactions  in  any  other  period  of  life.  There  is  a 
further  complexity  in  the  condition,  in  that  the  diseases  of  earlier 
life  have  produced  changes  which  may  accelerate  or  certainly 
complicate  the  development  of  those  changes  which  are  to  be 
regarded  as  physiological.  In  the  pathology  of  age  we  have  to  do 
with  lesions  which  are  imposed  upon  the  aged  organism  by  external 
causes.  Death  in  the  period  may  come  as  the  result  of  disease,  just 
as  at  any  other  period  of  life,  but  there  is  also  what  may  be  regarded 
as  physiological  death,  due  to  the  advancing  changes  becoming 
so  great  that  function  is  impossible.  There  is  great  individual  dif- 
ference in  the  period  of  development  and  in  the  rapidity  of  advance 
of  the  changes  of  age,  but  they  always  appear. 

Anyone  studying  the  subject  of  old  age  becomes  aware  of  the 
lack  of  knowledge  of  the  condition  when  he  seeks  in  literature 

918 


HEART  AND  KIDNEYS  OF  OLD  PEOPLE  919 

answers  to  the  questions  which  constantly  present  themselves,  and 
this  is  even  more  striking  in  the  study  of  old  age  in  animals.  There 
is  no  mammal  whose  life  history,  comprising  anatomy  and  physi- 
ology, we  know  from  beginning  to  end,  and  in  all  cases  we  know 
more  about  the  first  period  of  life  than  the  last.  We  do  not  know 
the  basic  metabolism  of  age  nor  whether  this  differs  from  the  metab- 
olism of  other  periods.  It  is  true  that  old  men,  impatient  of  the 
lack  of  consideration  and  interest  given  to  their  condition,  have 
written  of  the  philosophy  and  even  the  diseases  of  age,  and  though 
some  have  written  delightfully,  they  have  given  little  information. 
There  is  little  interest  in  the  condition  on  the  part  of  the  men  who 
have  both  the  ability  and  the  opportunities  for  investigation.  Old 
people  form  but  little  part  of  the  population  of  our  best  hospitals, 
and  the  chief  interest  in  the  last  thirty  years  has  been  rather  in  those 
diseases  and  conditions  to  which  the  old  are  relatively  immune. 

I  shall  present  in  this  paper  the  results  of  the  study  of  the  heart  and 
kidneys  in  the  autopsies  of  580  individuals  of  the  age  of  sixty  and  above. 
Of  these  cases  489  were  taken  from  the  records  of  the  Pathological  De- 
partment of  the  Harvard  Medical  School,  and  to  these  were  added  92 
cases  taken  from  Wideroe's  work  on  heart  weights.  The  records  from  the 
school  embrace  48  private  autopsies,  197  from  the  Boston  City  Hospital, 
148  from  Long  Island  Hospital,  and  95  from  the  Peter  Bent  Brigham  Hos- 
pital. All  these  groups  of  cases  show  certain  differences  regarding  age  at 
death,  weights  of  organs,  etc.,  but  these  are  all  within  the  variations  of 
chance,  and  a  greater  number  of  cases  would  probably  have  smoothed  out 
these  discrepancies.  There  is  always  difficulty  in  having  routine  patho- 
logical examinations  accurately  carried  out,  particularly  when  the  stimulus 
which  comes  from  close  correlation  between  clinical  and  pathological 
interest  is  lacking,  as  it  was  in  many  of  these  old  people.  In  most  cases 
the  histological  slides  of  the  autopsy  material  were  examined,  and  as  the 
result  of  this  a  few  changes  were  made  in  the  anatomical  diagnoses.  In 
the  cases  taken  from  Wideroe  only  the  ages  and  weights  of  organs  were 
accessible. 

The  age  of  sixty  plus  has  been  chosen  for  the  study,  because  at  this 

period  changes  are  always  present,  and  they  become  more  accentuated 

as  age  advances.  The  average  age  of  all  cases  is  sixty-nine.^  There  is  some 

difference  in  the  average  age  of  the  different  groups,  the  Boston  City 

Hospital  and  Peter  Bent  Brigham  Hospital  giving  sixty-six,  the  private 

>  In  the  figures  the  whole  numbers  to  which  the  decimals  most  closely  approximate 
are  given. 


930         HEART  AND  KIDNEYS  OF  OLD  PEOPLE 

autopsies  sixty-nine,  and  the  Long  Island  cases  seventy-two.  The  ex- 
pectation of  life  at  the  age  of  sixty  in  Massachusetts  is  13.4  for  males,  and 
14.8  for  females,  and  this  is  closely  approached  by  the  Long  Island  cases. 
This  institution  takes  care  of  a  large  number  of  aged  poor,  and  has  sent 
to  it  cases  of  chronic  disease  from  the  various  hospitals.  Wideroe's  cases 
from  Denmark  have  an  average  age  of  seventy-four,  and  his  material 
was  probably  rather  institutional  than  hospital. 

The  cases  by  age  fall  into  the  following  groups:  Sixty  to  sixty-nine, 
347  cases;  seventy  to  seventy-nine,  162  cases;  eighty  to  eighty-nine,  59 
cases;  ninety,  12  cases. 

The  Heart.  Hypertrophy  is  the  most  common  pathological  condition 
of  the  heart  at  these  ages,  and  a  primary  division  has  been  made  dependent 
upon  hypertrophy.  The  heart  was  removed  by  cutting  the  vessels  just 
inside  the  pericardium;  it  was  opened,  all  clots  removed,  and  weighed  with 
the  epicardial  fat.  The  amount  of  epicardial  fat  varies,  but  it  is  rarely 
sufficient  in  amount  to  place  a  smaller  heart  by  weight  in  the  class  of 
hypertrophy.  In  determining  hypertrophy,  350  grams  has  been  selected 
as  the  limit  of  normal  weight  in  the  female,  and  400  grams  in  the  male. 
The  weight  of  the  normal  heart  has  been  the  subject  of  many  investigations, 
the  most  extensive  being  that  of  Miiller,  in  which  all  epicardial  fat  was 
removed,  the  different  parts  of  the  heart — auricles,  ventricles,  and  septum 
— weighed  separately,  and  these  weights  compared  with  each  other  and 
the  body  weight.  It  is  impossible  to  establish  an  index  of  heart  weight  in 
relation  to  body  weight,  owing  to  the  variance  in  body  weight,  due  to  fat. 
The  heart  weight  is  influenced  by  the  muscular  development  of  the  body, 
and  the  fat  has  very  little  influence.  All  records  of  weights  of  the  normal 
heart,  with  the  exception  of  those  of  Miiller,  agree  that  there  is  a  gradual 
increase  of  weight  up  to  the  age  of  seventy,  from  which  there  is  a  slight 
decline.  Beneke,  who  has  made  volume  instead  of  weight  determinations, 
shows  that  the  volume  follows  the  same  law.  Thoma  gives  an  average 

*  Average,  Male 

Age  and  Female 

60  to  70 332 

70  to  80 321 

80  to  90 303 

Miiller's  weights,  taken  after  removal  of  fat,  are  very  irregular. 
Age  Male  Female 

401050 288.8  239.8 

50  to  60 277.6  229.9 

60  to  70 257.9  262.6 


HEART  AND  KIDNEYS  OF  OLD  PEOPLE 


921 


His  highest  weight  of  the  male  heart  is  between  the  ages  of  forty  and 
fifty,  and  of  the  female  between  sixty  and  seventy,  in  which  he  differs 
from  all  other  authors.  In  Doctor  Wolbach's  autopsies  of  26  young  soldiers, 
ages  twenty-one  to  thirty-one,  who  died  of  influenza  at  Camp  Devens, 
an  average  of  335  grams  was  found,  with  variations  between  245  and  425. 
That  350  grams  in  the  female  and  400  grams  in  the  male  are  outside  of  the 
normal  or  usual  variations  is  shown  by  the  small  number  of  weights  close 
beneath  these.  The  weights  do  not  gradually  increase  to  the  hypertrophic 
weight,  but  by  a  sharp  ascent.  In  the  females  there  were  21  cases  between 
320  and  350  grams,  and  in  the  males  26  between  360  and  400  grams. 

There  were  248  hypertrophied  hearts,  or  42.77  per  cent,  and  332 
non-hypertrophic.  The  weights  of  the  non-hypertrophied  hearts  are  by 
age: 


Males 

Females 

Male  and 
Female 

Age           1       Cases       |     Weights 

Cases       |     Weights         Average 

60  to  69       1           110         1           314 

88         1            282                     300 

70  to  79        1              47         1            315 

45         1            283                     299 

80  to  89        1              14         1            319 

19         1            267                     289 

90+                1                5         1            321 

4         1            294                     309 

The  hypertrophied  hearts  gave  the  following: 

Males 

Females 

Male  and 
Female 

Age           1       Cases       |     Weights 

Cases       |     Weights 

Average 

60  to  69        1              90         1            544 

59         1           514 

531 

70  to  79       1             40         1            491 

30         1           448 

473 

80  to  89       1              15         1            481 

11         1           440 

464 

90+                1                3         1            455 

455 

There  is  but  little  difference  in  the  relative  numbers  of  hypertrophied 
hearts  in  the  different  groups.  Wideroe's  cases  give  38  per  cent,  the  Peter 
Bent  Brigham  Hospital  44  per  cent,  the  private  autopsies  33  per  cent,  the 
Long  Island  Hospital  41  per  cent,  and  the  Boston  City  Hospital  50  per  cent. 
I  can  assign  no  reason  for  this  high  percentage  of  the  City  Hospital,  unless 
it  be  that  the  cases  going  to  this  hospital  represent  more  the  working  class 
of  the  population.  The  lowest  is  in  the  private  autopsies,  in  which  there 
is  but  small  representation  of  this  class. 

One  of  the  most  common  conditions  found  in  the  hearts  of  old  people 
is  valvular  sclerosis.  It  affects  both  aortic  and  mitral  valves,  is  rather  more 
frequent  in  the  former,  and  is  very  rare  in  the  right  heart.  It  consists  in 
foci  of  necrosis  with  fatty  and  calcareous  infiltration  of  the  valve,  and 
affects  chiefly  the  ventricular  aspect  of  the  mitral  valve  and  the  concave 


922  HEART  AND  KIDNEYS  OF  OLD  PEOPLE 

or  aortic  surface  of  the  aortic  valves.  The  aortic  segment  of  the  mitral  is 
most  frequently  affected,  but  there  is  no  preference  in  the  aortic  segments. 
In  the  mitral  it  is  often  associated  with  thickening  of  the  free  edge  of  the 
valve,  and  in  3  cases  there  was  calcification  of  the  ring  of  insertion.  It 
is  focal,  and  in  the  aortic  valves  begins  with  thickening  and  calcification 
of  the  line  of  insertion  from  which  there  is  extension  on  the  valves,  both 
continuously  and  in  small  foci.  The  affected  areas  are  opaque,  stiffer  than 
the  normal  valve  tissue,  and  when  calcified,  hard  and  brittle.  The  adjoining 
edges  of  the  aortic  cusps  may  become  adherent,  and  such  masses  of  lime 
salts  may  be  deposited  as  to  produce  stenosis.  It  is  difficult  to  differentiate 
between  this  purely  degenerative  condition  and  that  resulting  from  a 
healed  valvular  endocarditis.  I  have  regarded  as  healed  endocarditis  those 
cases  in  which  the  condition  was  associated  with  thickening  and  shortening 
of  the  chordae  tendineae  of  the  mitral  and  irregular  thickening  and  retraction 
of  the  aortic  valves.  The  condition  is  not  to  be  confounded  with  the  exten- 
sion of  a  syphilitic  aortitis  to  the  aortic  valves.  There  were  but  2  cases 
of  this,  and  in  general  evidence  of  syphilis  is  rare  at  these  ages.  Such 
valvular  sclerosis  was  found  in  77  cases,  42  of  these  with  heart  hypertrophy, 
35  without.  In  16  of  the  cases  it  was  extensive  enough  to  produce  stenosis 
of  the  aortic  orifice,  and  in  all  of  these  there  was  hypertrophy.  In  42  cases 
of  chronic  endocarditis  there  was  hypertrophy  in  25  cases.  In  5  of  the 
cases  there  was  sufficient  thickening  and  retraction  of  the  mitralasobviously 
to  interfere  with  function,  and  in  3  of  these  the  heart  was  hyj)ertrophied. 
There  were  16  cases  of  acute  endocarditis,  2  of  these  ulcerative  and  3 
verrucous,  the  others  were  terminal  and  consisted  of  thrombi,  usually 
minute,  on  the  edges  of  the  valves  in  association  with  infection  elsewhere. 
The  Myocardium.  I  have  not  considered  the  many  cases  of  fatty  de- 
generation. It  is  a  pathological  condition,  and  certainly  in  its  highest  degree 
indicates  injury  of  the  fibers  most  affected,  but  there  is  no  clear  evidence 
that  it  produces  permanent  injury,  nor  does  it  seem  to  interfere  with 
function.  It  was  as  common  in  the  hypertrophied  as  in  the  non-hypertro- 
phied  cases,  and  in  general  its  frequency  depends  upon  the  care  with  which 
it  is  sought.  There  was  i  case  of  acute  myocarditis  with  miliary  abscesses, 
due  to  staphylococcus.  Fibrous  myocarditis  was  diagnosed  in  86  cases,  of 
which  60  were  in  the  hypertrophied  hearts,  and  varied  in  degree  from 
small  foci  to  large  areas  in  which  the  entire  thickness  of  the  wall  was  sut>- 
stituted  by  fibrous  tissue.  In  3  of  these  there  was  globular  dilatation  of  the 
heart  at  the  affected  area,  constituting  heart  aneurysm.  Some  of  the  foci 
were  recent,  and  necrotic  fibers  were  found  invaded  by  leucocytes,  and  in 
nearly  all  cases  the  adjoining  muscle  fibers  were  atrophic  with  diminution 
of  fibrillae.  Generally  in  the  hypertrophied  hearts  the  fibers  were  large. 


HEART  AND  KIDNEYS  OF  OLD  PEOPLE         923 

and  the  fibrillae  seemed  not  reduced  in  number.  In  3  cases  of  hypertrophy 
fibers  were  found  which  showed  an  unduly  large  amount  of  sarcoplasm 
with  reduction  of  fibrillae,  the  condition  described  by  Albrecht.  In  these 
cases  there  was  much  fibrous  myocarditis,  though  not  immediately  asso- 
ciated with  the  affected  fibers. 

It  was  not  possible  to  refer  the  fibrous  myocarditis  to  circulatory 
disturbance  due  to  arteriosclerosis  of  the  coronary  arteries.  Where  the 
foci  were  large,  particularly  those  at  the  apex  of  the  left  ventricle,  occlusion 
of  the  branch  of  the  coronary  which  supplied  the  area  was  usually  found. 
It  was  found  associated  with  extensive  disease  of  the  coronaries,  but  also 
when  the  arteries  were  but  slightly  affected  and  extensive  coronary  sclerosis 
may  coincide  with  a  normal  myocardium.  There  seems  no  doubt  that 
fibrous  myocarditis  is  very  frequently  due  to  degeneration  of  the  muscle 
from  lack  of  blood  supply,  and  slowly  advances,  but  much  of  it  is  the  final 
result  of  myocardial  injury  associated  with  inefction.  Infarction  of  the 
heart  was  found  in  13  cases,  and  in  7  of  these  there  was  rupture.  In  all  of 
these  cases  the  wall  of  the  left  ventricle  was  affected,  and  either  thrombosis 
or  complete  sclerotic  closure  of  the  corresponding  coronary  artery  was 
found.  Eight  of  the  cases  were  in  hypertrophied  hearts. 

In  8  cases  the  heart  weighed  less  than  200  grams,  and  all  these  were  in 
the  decade  from  sixty  to  sixty-nine,  the  smallest,  125  grams,  was  in  a  small 
emaciated  woman  who  had  long  been  bedridden,  and  in  none  was  there 
marked  disparity  between  the  size  of  the  heart  and  that  of  the  body. 
There  were  several  cases  of  tumor  metastasis  in  the  heart,  and  i  case  in 
which  it  was  displaced  by  the  advance  of  a  carcinoma  of  the  lung.  In  some 
cases  of  general  edema  there  was  also  edema  of  the  myocardium  with 
vacuolization  of  the  fibers. 

There  were  46  cases  of  pericarditis,  29  of  which  were  in  the  hyper- 
trophied class,  and  14  of  the  cases  were  acute.  There  were  also  8  cases  of 
hydropericardium  due  to  circulatory  disturbance,  7  of  which  were  in  the 
hypertrophied  class. 

In  spite  of  the  many  pathological  conditions  which  can  be  named,  on 
the  whole  the  heart  in  old  people  is  a  very  good  organ,  and  anatomically 
has  suffered  less  from  injury  and  wear  than  any  of  the  large  internal 
organs. 

The  Kidneys.  The  normal  kidney  varies  considerably  in  weight,  and 
the  estimates  of  weight  also  vary.  Thoma  gives  306  grams  as  the  average. 
Of  his  cases  50  were  between  269  and  306,  and  50  between  306  and  343. 
Wideroe's  cases,  at  ages  from  twenty-five  to  fifty  years,  give  for  males 
319  and  females  306,  an  average  of  313.  Orth  gives  320  for  males  and  293 
for  females.  Wolbach  has  found  in  26  autopsies  on  young  soldiers,  ages 


924 


HEART  AND  KIDNEYS  OF  OLD  PEOPLE 


twenty-one  to  thirty-one,  who  died  of  influenza,  an  average  weight  of 
356,  with  variations  from  150  to  460  grams.  There  were,  however,  patho- 
logical conditions  which  caused  some  increase  in  weight.  The  average 
weight  in  the  cases  considered  here  is  269  grams.  This  diminution  in  weight 
does  not  fairly  represent  the  degree  of  atrophy.  Cysts  of  the  cortex  are 
common  and  numerous;  there  is  often  considerable  formation  of  fat  in  the 
pelvis  following  atrophy,  often  more  or  less  thickening  and  adhesion  of  the 
capsule,  and  the  weights  of  the  large  kidneys  showing  pyelonephrosis  are 
included  in  the  average  weight.  There  is  considerable  decline  in  weight  as 
age  advances,  with  the  exception  of  extreme  age,  when  the  weight  of 
the  kidneys,  like  that  of  the  heart,  increases.  There  is  also  considerable 
diff"erence  in  the  weights  of  the  cases  with  hypertrophied  hearts. 


Heart  Hypertrophy 

Non-Heart 

Hypertrophy 

Age 

Cases 

Weights 

Cases 

Weights 

60  to  69 

143 

317 

191 

264 

70  to  79 

68 

275 

89 

233 

80  to  89 

25 

229 

32 

221 

90+ 

3 

265 

9 

233 

Total  cases 

239 

321           1 

Average  weight 

1           295 

1           250 

It  is  probable  that  some  of  the  diff"erence  in  weight  of  the  hypertrophic 
cases  is  due  to  the  more  general  prevalence  of  passive  congestion  in  these. 
There  are  few  conditions  which  so  generally  repeat  themselves  as  does 
that  of  the  kidneys  in  old  age.  The  capsule  is  usually  slightly  thickened  and 
adherent,  the  surface  beneath  rarely  smooth,  usually  finely  granular,  but 
the  granulation  is  not  so  marked  as  in  the  genuine  small  granular  kidney. 
There  may  be  definite  losses  of  substance  due  to  old  infarctions  or  other 
focal  pathological  conditions,  but  the  coarse  and  irregular  depressions 
generally  regarded  as  characteristic  of  the  arteriosclerotic  kidney  are  not 
frequently  found.  On  section  the  markings  are  not  so  evident  as  in  the 
normal,  both  cortex  and  pyramids  are  reduced,  the  tissue  is  more  lax,  but 
tougher  than  normal,  and  cannot  be  broken  on  bending.  Microscopically 
there  are  areas  of  atrophy  and  destruction  involving  both  tubules  and 
glomeruli,  which  are  usually  focal  and  close  beneath  the  capsule.  They 
are  small,  triangular,  with  a  broad  base  on  the  surface,  and  they  rarely 
extend  through  the  cortex.  The  epithelium  of  the  cortical  tubules  is  low, 
is  less  granular  than  normal,  the  tubules  appear  dilated,  the  nuclei  are 
small,  contain  less  chromatin,  and  are  fewer  in  number  in  the  syncitium. 
In  other  parts  of  the  cortex  there  are  single  destroyed  glomeruli 
and  some  small  areas  of  atrophic  tubules.  Measurements  of  glomeruli 
show  diminution  in  size,  and  single  groups  of  vessels  in  a  glomerulus 


HEART  AND  KIDNEYS  OF  OLD  PEOPLE         925 

become  obsolete.  The  pyramids  are  smaller,  the  striation  lost,  and 
microscopically  the  interstitial  tissue  has  lost  its  fibrillation,  is  hyaline, 
but  still  gives  the  collagen  stain.  There  is  often  extensive  destruction 
of  the  pyramidal  tubules,  forcing  the  conclusion  that  in  some  way 
new  arrangements  of  tubules  must  have  taken  place.  In  every  kidney 
examined  casts  were  found  in  the  tubules,  usually  in  the  Henle  or  small 
collecting  tubules  at  the  base  of  the  pyramids,  sometimes  numerous,  at 
other  times  few.  This  condition  of  the  kidney  I  have  designated  chronic 
atrophic  nephropathy,  and  it  is  as  characteristic  of  age  as  is  the  shrunken 
shank  and  tottering  gait.  After  studying  these  cases,  to  take  up  the  sec- 
tions which  Dr.  Wolbach  has  made  from  the  kidneys  of  young  soldiers 
gives  the  impression  of  passing  from  age  to  youth.  I  have  found  this 
condition,  which  in  the  protocols  was  variously  described  as  chronic 
interstitial  nephritis,  senile  nephritis,  arteriosclerotic  nephritis,  vascular 
nephritis,  etc.,  in  246  cases,  124  of  these  with  hypertrophied  hearts.  Of 
the  other  forms  of  hematogenous  nephropathy  there  was  i  of  acute  glom- 
erular nephropathy  and  6  of  subacute  and  chronic — all  of  these  in  the 
heart  hypertrophy  class,  and  7  cases  of  small  granular  contracted  kidney, 
2  of  which  were  in  the  non-heart  hypertrophy  series.  The  total,  13,  oc- 
curred in  the  decade  sixty  to  sixty-nine  years.  There  were  36  cases  of  pye- 
litis and  pyelonephrosis,  9  cases  of  hydronephrosis,  all  in  association  with 
prostatic  disease,  and  6  of  nephrolithiasis;  27  of  all  these  conditions  were 
in  the  non-hypertrophic  class. 

In  certainly  three-fourths  of  all  cases  examined  sclerosis  of  the  renal 
arteries,  varying  in  degree  and  extent,  was  present.  In  certain  cases  it  was 
most  marked  in  the  arcuate  arteries,  in  others  in  the  interlobular  and  the 
glomerular  branches,  and  in  others  all  were  affected.  The  evident  condition 
in  these  arteries  was  atrophy  and  destruction  of  the  media  with  increase 
in  the  intima.  In  some  arteries  it  was  distinctly  focal,  in  others  the  entire 
wall  was  equally  affected,  the  artery  represented  by  a  small  lumen  sur- 
rounded by  a  hyaline  mass,  the  media  having  completely  disappeared. 
The  elastica  in  most  cases  shared  the  fate  of  the  muscularis,  in  others  the 
elastic  lamina  was  split  and  formed  a  series  of  concentric  circles  in  the 
hyaline  masses.  As  far  as  it  was  possible  to  determine,  the  atrophy  and 
destruction  of  the  media  was  primary,  always  more  marked  near  the 
internal  surface,  and  the  changes  in  the  intima  were  proportional  to  the 
medial  injury.  The  caliber  generally  seemed  reduced  in  size,  often  irregular, 
but,  of  course,  such  examination  can  give  us  no  information  of  the  caliber 
during  life.  Associated  with  these  arterial  changes  there  were  glomerular 
changes  consisting  in  thickening  of  the  capillary  walls  of  single  vessels  or 
groups,  gradually  involving  the  entire  structure.  The  minute  arteries  were 


926         HEART  AND  KIDNEYS  OF  OLD  PEOPLE 

affected  to  a  much  greater  degree  than  the  main  stem,  which  was  often 
free  from  lesion.  It  is  impossible  to  see  these  vascular  lesions,  producing, 
as  they  must,  interference  with  the  circulation  and  thereby  disturbing 
nutrition  and  function,  without  holding  them  accountable  for  at  least  a 
part  of  the  renal  change.  There  are  certain  conditions,  however,  which 
make  the  matter  uncertain.  The  coronary  arteries  of  the  heart  are  very 
generally  affected  in  old  age,  and  although  fibrous  myocarditis  is  often 
present,  no  definite  relation  exists  between  this  and  the  vascular  disease. 
It  is  further  true  that  the  main  coronary  vessels  are  affected  to  a  greater 
degree  than  the  small  penetrating  branches,  while  the  reverse  is  true  in  the 
kidneys.  In  the  arteriosclerosis  of  younger  individuals  there  may  be  ex- 
tensive changes  in  the  renal  arteries  without  the  lesions  so  characteristic 
of  the  old.  Old  dogs,  in  whom  arteriosclerosis  can  practically  be  excluded, 
,  have  atrophic  lesions  of  the  kidneys  involving  both  tubules  and  glomeruli, 
but  they  differ  in  kind  from  the  changes  in  the  human  kidney.  No  vessels 
in  the  body  are  so  free  from  disease  as  in  the  liver,  and  yet  here  there  is  in 
old  age  atrophy  of  parenchyma  and  increase  in  fibrous  tissue.  It  is  absurd 
to  attempt  to  refer  old  age  to  arteriosclerosis,  and  yet  anyone  studying 
these  kidneys,  in  which  the  vascular  lesions  are  so  general  and  so  striking, 
would  almost  certainly  regard  them  as  the  primary  and  essential  factor. 

Through  the  courtesy  of  Dr.  H.  A.  Christian  I  am  enabled  to  give  the 
records  of  the  blood  pressure  in  the  Peter  Bent  Brigham  Hospital  cases, 
omitting  one  case  of  very  high  pressure  due  to  intracranial  tumor. 

HYPERTROPHIC  CASES 

Male | Female |         General  Average 

Systolic      I     Diastolic     |       Systolic        |     Diastolic     |       Systolic       |     Diastolic 
160  I  87  I  153  I  90  I  158  I  88        ~ 

Extremes 
(Disregarding  one  case  of  cerebral  tumor.) 


1         Systolic 

1        Diastolic 

High 

1             235 

1             160 

Low 

1               90 

1               40 

NON-HYPERTROPHIC  CASES 


Male | Female |  General  Average 

Systolic      I     Diastolic     |       Systolic        |     Diastolic     |       Systolic       |     Diastolic 
127  I  "        78  I  134  I  77  |  130  |  78 


Extremes 

1         Systolic         1 

Diastolic 

High 

1             195             1 

100 

Low 

1               60             1 

30 

HEART  AND  KIDNEYS  OF  OLD  PEOPLE         927 

These  figures  do  not  differ  essentially  from  those  given  by  others. 
Woley  gives  138  systolic  as  the  average  at  the  ages  sixty  to  sixty-five. 
Weldt  has  found  that  from  sixty  to  ninety  years  the  systolic  pressure 
increases  from  137  to  190,  but  after  ninety  the  pressure  gradually  falls. 

Conclusions.  The  main  interest  which  has  come  from  the  study 
of  these  cases  is  the  demonstration  of  the  great  frequency  of  heart 
hypertrophy  in  old  people.  I  regard  it  as  pathological,  due  to  some 
unusual  conditions,  and  not  as  a  part  of  the  physiological  changes 
of  age.  It  is  as  difficult  to  give  any  adequate  explanation  of  heart 
hypertrophy  in  the  old  as  it  is  to  explain  the  condition  at  any  period 
of  life.  The  whole  question  of  muscular  hypertrophy  is  obscure.  The 
mechanical  explanation  that  the  heart  meets  continued  opposition 
to  the  passage  of  blood  through  or  from  it  by  acquiring  greater 
power  through  increase  of  muscular  substance,  and  that  this  is  the 
essential  cause  of  all  hypertrophies,  though  no  longer  so  firmly  held 
as  it  was  twenty-five  years  ago,  is  adequate  in  certain  cases.  Hyper- 
trophy does  take  place  in  all  cases  of  aortic  stenosis  and  insufficiency 
at  any  period  of  life.  It  also  takes  place  in  certain  cases  where  the 
peripheral  resistance  is  increased.  It  takes  place,  I  think,  always  in 
the  cases  of  subacute  and  chronic  glomerulonephropathy,  in  which 
cases  there  is  a  maximum  interference  with  the  circulation  through 
the  kidney.  The  mere  reduction  in  the  amount  of  renal  tissue  even 
in  cases  in  which,  like  hydronephrosis,  there  would  seem  to  be  cir- 
culatory obstruction,  may  or  may  not  be  associated  with  hyper- 
trophy. The  influence  of  arteriosclerosis  of  the  aorta  and  its  main 
branches  in  producing  hypertrophy  may  be  disregarded.  In  these 
cases  it  was  always  present,  and  there  was  no  relation  to  heart 
hypertrophy  in  the  degree  and  extent  of  the  arterial  changes.  When 
I  began  the  study  of  these  cases  I  thought  there  was  a  relation 
between  heart  hypertrophy  and  that  type  of  arteriosclerosis  of  the 
renal  arteries  in  which  the  interlobular  arteries  and  the  glomerular 
branches  were  aff"ected.  For  a  time  I  was  successful  in  naming  the 
condition  of  the  heart  from  the  examination  of  the  kidney  sections, 
but  finally  mistakes  were  so  frequent  as  to  show  that,  while  this 
relation  is  frequent,  it  is  far  from  being  universal.  It  has  been 
assumed  by  some,  notably  by  MacKenzie,  that  the  increased  blood 
pressure  of  age  is  due  to  reduction  of  the  capillary  area  of  the 
cutaneous  circulation,  but  though  it  is  evident  from  the  senile 


928         HEART  AND  KIDNEYS  OF  OLD  PEOPLE 

changes  of  the  skin  that  there  is  a  reduction  of  the  capillary  area, 
it  is  as  evident  in  the  nonhypertrophies  as  in  the  hypertrophies. 
There  is  need  in  all  these  obscure  cases  of  hypertrophy  of  the  heart 
of  a  much  more  thorough  study  of  terminal  arteries  and  capillaries 
than  was  possible  in  the  cases  here  reported.  The  heart  in  old  age, 
as  in  all  periods  of  life,  is  a  good  mechanism,  and  it  does  not  fail, 
but  is  even  capable  of  increasing  its  capacity  for  work  when  the 
other  machines  of  the  body  are  slacking  in  their  efforts. 


EPIDEMIOLOGY  OF  POLIOMYELITIS 
By  Simon  Flexner,  M.D. 

(From  the  Laboratories  of  The  Rockefeller  Institute  for  Medical  Research,  New  York) 

THE  severe  epidemics  of  p)oIiomyeIitis  of  the  past  fifteen  years 
have  established  a  new  world  record.  They  have  served  also 
to  bring  into  the  foreground  of  medical  discussion  the  epi- 
demiology of  the  disease. 

The  series  of  epidemics  alluded  to  may  be  considered  to  date 
from  the  Norwegian  and  Swedish  outbreaks  of  1903  to  1905.  Pre- 
vious to  those  occurrences,  occasional  foci  of  cases  of  poliomyelitis 
appeared  in  widely  separated  localities  in  Europe  and  the  United 
States,  but  no  wide  spread  of  the  disease  resulted  from  those  foci. 

The  Norwegian  and  Swedish  epidemics,  and  particularly  the 
epidemic  of  1905,  appear  to  be  the  immediate  forerunners  of  the 
pandemic  which  prevailed  from  1907  to  1909  in  Europe  and  America. 
Subsequently  the  disease  reappeared  in  epidemic  form  in  Scandi- 
navia in  191 1  and  191 3.  In  the  United  States  the  pandemic  of  1907  to 
1909  left  behind  either  small  local  foci  of  poliomyelitis,  or,  what  was 
more  frequent,  conditions  favoring  a  greater  incidence  of  the  sp>oradic 
disease  than  had  previously  been  noted. 

This  was,  in  brief,  the  situation  until  19 16,  when  an  outburst  of 
the  disease  of  unparalleled  severity  overwhelmed  the  North  Atlantic 
region  of  the  United  States.  The  storm  center  of  the  epidemic  wave 
was  New  York  City  and  the  adjacent  regions  of  New  York  State, 
Connecticut,  and  Massachusetts.  The  epidemic  was  not  confined 
to  the  Northeastern  States,  but  in  far  less  degree  involved  the  Middle 
and  Southern,  and  even  the  far  Western  States.  The  rep>orted  cases 
in  New  York  State  as  a  whole  exceeded  20,000;  but  it  is  improbable 
that  even  that  great  figure  really  includes  all  the  cases  which  arose 
between  May,  when  the  first  five  cases  were  rep>orted  in  New  York 
Gty,  and  November,  at  which  time  the  usual  incidence  seems  to 
have  been  re-established.  The  diagram  (Fig.  i)  gives  an  approxi- 
mate indication  of  the  distribution  of  the  epidemic  foci  of  19 16. 

929 


930 


EPIDEMIOLOGY  OF  POLIOMYELITIS 


As  registration  is  unequal  in  dijfferent  sections  of  the  country,  it  is  to 
be  assumed  that  the  occurrences  are  under  rather  than  overstated. 
But  what  is  particularly  remarkable  is  the  fact  that,  notwith- 
standing the  unequaled  intensity  of  the  191 6  outbreak  in  the  Atlantic 
coast  region  and  partial  dissemination  of  the  malady  in  the  interior 
of  the  United  States,  the  greater  part  of  the  country  escaped  attack, 
and  the  disease  failed  to  reappear  in  force  in  19 17  or  subsequently 
up  to  the  present  writing  (April,  19 19).  In  other  words,  the  very 


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Shaded  Areas  Show  Lxjcalities  Particularly  Involved  in  the  Poliomyelitis 

Epidemic  of  1916. 

fury  of  the  epidemic  disease  seems  to  have  brought  about  rapid 
exhaustion  of  its  striking  power. 

This  last  phenomenon  is  met  with  in  some  degree  with  epidemics 
generally;  it  is  the  peculiarly  impressive  quality  of  this  instance 
which  specially  arrests  attention.  It  is  of  interest  to  observe  that  in 
New  York  City,  where  by  far  the  greatest  number  of  cases  was 
massed  together,  the  incidence  was  1.59  per  thousand  of  population, 
and  83  per  cent  of  all  reported  cases  were  in  children  under  five 
years  of  age.  In  many  parts  of  the  United  States  the  attack  rate  was 
far  below  that  of  New  York  City.  And  yet  the  epidemic  abated 
during  the  autumn  of  191 6  and  has  not  yet  recurred.  Hence  it  would 


EPIDEMIOLOGY  OF  POLIOMYELITIS  931 

seem  that  the  factors  governing  the  attack  rate  and  those  affecting 
the  rise  of  the  epidemics  may  be  quite  dissimilar. 

In  seeking  an  explanation  for  the  attack  rate,  we  easily  fall  back 
upon  those  general,  if  vague,  principles  of  susceptibility  which  appear 
everywhere  to  operate  in  promoting  or  preventing  infection;  or  we 
incline  towards  the  notion,  as  yet  quite  hypothetical,  of  a  state  of 
rapid  and  wide  immunization  of  communities  through  inappreciably 
mild  attacks  of  disease.  The  relatively  recent  knowledge  and  impli- 
cations of  the  carrier  state  have  made  this  idea  easily  acceptable. 

The  conception  that  the  incidents  leading  to  the  peculiar  curve 
of  the  epidemics  of  poliomyelitis  are  brought  about  by  wide  dis- 
semination of  the  microbic  agent  of  the  disease  through  abortive 
cases  and  healthy  carriers  has  been  several  times  advanced,  for 
example  by  Kling,  Pettersson,  and  Wernstedt,  (i)  who  studied 
the  Swedish  epidemics  of  the  years  between  1905  to  191 1,  and  by 
Wernstedt,  (2)  who  studied  the  epidemic  of  191 1.  It  has  again  been 
invoked  by  Lavinder,  Freeman,  and  Frost,  (3)  who  made  an  epidemi- 
ological study  of  the  19 16  epidemic  in  the  Northeastern  part  of  the 
United  States.  The  latter  authors  state  in  effect  that  an  incidence 
of  one  to  three  recognized  cases  per  thousand,  or  even  less,  immun- 
izes the  general  population  to  such  an  extent  that  the  outbreaks 
decline  spontaneously,  due  to  exhaustion  or  thinning  out  of  the  infec- 
tible  material.  In  like  manner,  they  conceive  that  communities 
visited  by  a  few  cases  may  be  preserved  from  a  severe  visitation  at 
a  later  period  at  which  the  epidemic  is  prevailing  elsewhere  in  fresh 
territory. 

Our  views  on  the  epidemiology  of  poliomyelitis  are  based  largely 
on  statistical  observations  and  very  little  on  experimentally  veri- 
fiable data.  Mere  statistical  observations  have  led  to  the  notion  so 
generally  accepted  that  poliomyelitis  is  strictly  a  seasonal — late 
summer  and  autumn — disease.  The  fact  is  that  outbreaks  of  some 
dimensions  have  repeatedly  taken  place  in  the  winter  in  Scandinavia; 
recently  a  midwinter  outbreak  occurred  in  the  United  States  in  and 
about  Fairmont,  W.  Va.  Epidemic  poliomyelitis  and  epidemic  cere- 
brospinal meningitis  have  been  not  infrequently  confounded  with 
each  other.  As  the  latter  disease  tends  to  prevail  in  the  winter  and 
early  spring  months,  a  more  precise  clinical  study  might  not  improb- 
ably show  that  at  times  the  latter  is  mistaken  for  the  former. 


932  EPIDEMIOLOGY  OF  POLIOMYELITIS 

II.  It  is  commonly  supposed  that  epidemics  of  poliomyelitis  arise 
at  given  places  through  the  importation  from  another  region,  near 
or  remote,  of  specimens  of  the  microbic  agent  or  virus  of  height- 
ened virulence.  We  possess,  indeed,  conclusive  evidence  that  this 
virus  undergoes  a  remarkable  increase  in  activity  through  mere 
passage  from  individual  to  individual. 

That  is,  by  successive  passages  of  human  strains  of  the  virus 
through  monkeys,  a  high  degree  of  virulence  may  be  attained  for 
that  species.  How  great  the  changes  are  that  take  place  can  be  in- 
ferred only,  since  in  the  inoculation  of  filtered  extracts  of  the  nervous 
organs  we  cannot  actually  measure  the  number  of  micro-organisms 
introduced.  The  rise  in  virulence  is  shown  not  only  by  the 
smaller  effective  dose,  but  also  by  the  circumstance  that  while  at 
the  beginning  of  the  adaptation  the  proportion  of  monkeys  devel- 
oping paralysis  is  smaller  and  the  number  of  recoveries  after  paraly- 
sis larger  than  at  a  later  period,  once  the  adaptation  has  been  ac- 
complished all  the  animals  inoculated  tend  to  become  paralyzed 
and  succumb  to  the  disease. 

Once  acquired,  this  state  of  high  virulence  is  retained  over  a  long 
period  of  time;  whether  it  becomes  a  fixed  quality  has  not  hitherto 
been  known.  This  latter  point  is  of  fundamental  importance.  It 
now  appears  (4)  that  a  particular  strain  of  the  poliomyelitic  virus 
which  had  acquired  high  virulence  and  maintained  it  for  a  period 
of  three  years,  during  which  it  was  passed  successively  through 
macacus  rhesus  monkeys,  had  undergone  successive  deterioration  of 
activity,  until  it  about  returned  to  the  degree  of  infecting  power  cor- 
resf>onding  to  that  which  it  possessed  in  the  original  human  material. 

It  is  possible  to  apply  this  experimental  demonstration  to  the 
interpretation  of  the  salient  epidemiological  phenomena  of  pohomye- 
litis.  Thus,  at  the  outset,  the  virus  of  pohomyeHtis  possesses  relatively 
weak  pathogenic  action  in  monkeys.  By  means  of  a  few  passages, 
the  infective  power  rises  and  soon  a  maximum  is  reached  which 
endures  for  some  time.  Ultimately  the  infective  power  falls  off  and 
soon  becomes  greatly  diminished,  so  that  finally  the  power  is  no 
greater  than  at  the  outset.  This  succession  of  changes  dependent  on 
alterations  of  virulence  finds  a  counterpart  in  the  phenomena  noted 
during  the  rise,  persistence,  then  fall  of  the  number  of  cases  that 
constitute  epidemics  of  the  disease.  Moreover,  the  fluctuations  in 


I 


EPIDEMIOLOGY  OF  POLIOMYELITIS  933 

virulence  depend,  as  far  as  can  be  seen,  on  causes  acting  on  the 
virus  from  within  the  body  of  the  animals,  which  causes,  whatever 
their  nature,  operate  to  produce  a  cycle  of  activity  indicated  by 
rise,  fixation,  and  decline  in  infecting  power.  And  this  is  the  cycle, 
apparently,  that  many  epidemics  pass  through  in  the  course  of  their 
appearance  and  disappearance. 

That  the  virus  of  poliomyelitis  is  communicated  by  personal 
contact  is  now  generally  admitted;  and  that  it  occurs  in  the  naso- 
pharynx, which  constitutes  the  chief  locus  of  ingress  and  egress  to 
and  from  the  body,  is  also  conceded.  The  fact  that  the  virus  has  in  a 
very  few  instances  been  detected  in  healthy  persons  who  have  been 
in  intimate  contact  with  early  cases  of  poHomyelitis,  and  even  in 
certain  individuals  who  have  recovered  from  the  acute  effects  of 
the  disease,  has  led  to  the  generalization  that,  like  some  other  dis- 
eases of  bacterial  origin,  and  notably  epidemic  meningitis,  healthy 
and  chronic  carriers  of  the  virus  are  frequent.  This  view  has  received 
its  main  support  from  Kling,  Pettersson,  and  Wernstedt.  A  critical 
analysis  of  the  basis  of  their  contention  fails,  however,  to  carry  con- 
viction. 

The  inadequacy  of  their  data  is  made  more  probable  by  the  experi- 
ments made  with  excised  pharyngeal  and  nasal  tissues  taken  either 
post-mortem  or  removed  surgically  during  life.  (5)  The  two  sets  of 
tissues,  those  removed  at  autopsy  and  those  removed  during  life, 
differed  in  one  essential  respect.  The  former  came  from  cases  of 
poliomyelitis  in  the  first  week,  and  the  latter  later  in  the  course  of 
the  disease.  On  the  basis  of  infectivity  the  deduction  seemed  war- 
ranted that  the  nasal  and  pharyngeal  mucosae  of  persons  succumbing 
to  polyomyelitis  during  the  first  ten  days  of  the  disease  probably 
regularly  contain  the  virus,  while  the  virus  diminishes  relatively 
quickly  as  the  disease  progresses,  except  in  rare  instances;  and  it  is 
unusual  for  a  carrier  state  to  be  developed. 

Available  evidence  proves  that  healthy  carriers  of  the  virus 
occur.  We  do  not,  however,  p>ossess  data  which  indicate  the  fre- 
quency with  which  carriage  arises.  The  fact  that  even  after  a  severe 
and  wide  epidemic,  such  as  occurred  in  the  United  States  in  1916, 
the  disease  may  virtually  disappear  in  two  or  three  years,  p>oints  to 
the  probability  that  enduring  carriers  of  the  virus,  whether  healthy 
or  chronic,  are  of  exceptional  occurrence. 


934 


EPIDEMIOLOGY  OF  POLIOMYELITIS 


To  the  two  factors,  namely,  that  the  microbic  agent  or  virus  of 
poliomyelitis  fluctuates  in  virulence  and  tends  rapidly  to  disappear 
from  the  upper  respiratory  mucous  membrane  during  convalescence, 
may  be  attributed  certain  striking  features  of  the  epidemiological 
history  of  the  disease. 


BIBLIOGRAPHY 

1.  Kling,  C.,  Pettersson,  A.,  ^and  Wernstedt,  W.,  "Communications  de 

rinstitut  Medical  de  I'Etat  k  Stockholm,"  1912,  261. 

2.  Wernstedt,  W.,  ibid.,  264. 

3.  Lavinder,  C.  H.,  Freeman,  A.  W.,  and  Frost,  W.  H.,  Pub.  Health  Bull., 

Washington,  No.  91,  July,  19 18. 

4.  Flexner,  S.,  Clark,  P.  F.,  and  Amoss,  H.  L.,  J.  Exper.  M.,  1914,  XIX,  45. 

5.  Flexner,  S.,  and  Amoss,  H.  L.,  J.  Exper.  M.,  1919,  XXIX,  379. 


HEMANGIOENDOTHELIOMA  OF  THE  LIVER  IN  THE 
INFANT,  AND  SO-CALLED  ANGIOSARCOMA 

By  John  Foote,  M.D.,  Washington,  D.  C. 

(From  the  Pediatric  Wards  of  Providence  Hospital  and  the  Department  of  Pediatrics, 
Georgetown  University  Medical  School) 

PRIMARY  adenoma,  cavernoma,  and  sarcoma  of  the  liver  are 
not  unusually  rare  even  in  early  life.  StefFen's  collection  of 
tumors  in  childhood,  (i)  Knott's  (2)  article  on  primary  sarcoma 
of  the  liver  with  protocols  of  seventy  cases,  and  numerous  isolated 
case  reports  from  French,  Russian,  and  especially  Italian  patholo- 
gists bring  the  occurrence  of  these  growths  quite  outside  the  range 
of  singularity. 

The  simple  or  solitary  angiomas  of  the  liver,  though  relatively 
frequent  in  adult  autopsies,  are  far  from  common  in  children; 
Kaufmann,  (3)  Michailow,  (4)  Steflfen,  (i)  Gatewood  (5)  and  others 
have  reported  these  formations,  but  Gatewood  could  find  less 
than  a  score  in  all. 

The  rarest  of  all  primary  tumors  of  the  liver  in  infancy  are  the 
hemangioendotheliomas;  almost  as  infrequent  are  hemangiosar- 
comas.  That  angiomas  of  the  skin  and  multiple  angiomas  of  the  liver 
may  assume  an  endothelial  sarcoma  type  has  been  pointed  out  in 
adult  cases  by  Dutton  (6)  and  Fischer  (7).  But  although  the  rapidly 
growing  hemangioendotheliomas  of  the  liver  in  infants  have  been 
named  by  some  observers  endotheliomas  and  by  others  sarcomas, 
they  are  so  similar  in  history,  chnical  course,  and  gross  anatomy 
as  to  constitute  a  distinct  clinical  entity  among  the  disorders  of 
early  life  sufficient  to  strengthen  still  further  the  anatomical  evidence 
in  adult  tumors  of  the  identity  of  the  two  conditions. 

The  following  case  history  from  the  Pediatric  Department  of 
Providence  Hospital,  Washington,  D.  C,  is  typical. 

Case  No.  4620.  Male  child  three  months  old,  referred  by  Dr.  R.  Pyles 
for  obstinate  constipation  suggesting  intestinal  obstruction.  Was  born  at 
full  term  and  breast  fed  until  two  weeks  before  entry.  Constipation  began 

935 


936      HEMANGIOENDOTHELIOMA  OF  THE  LIVER 

when  two  months  old;  enlargement  of  abdomen  also  noticeable  at  this 
time.  ISo  bowel  movement  in  last  seventy-two  hours. 

Examination.  Fairly  well-nourished  child,  prominent  abdomen,  intes- 
tines distended.  Liver  edge  irregular,  7  cm.  below  costal  margin  in  mam- 
mary line.  A  mass  in  abdomen  extending  toward  back  reaching  to  iliac 
crest  on  right  side.  (Wassermann  negative  in  both  parents.) 

Exploratory  laparotomy  by  Dr.  Harrison  Crook  showed  a  large  liver, 
purplish  in  color  with  numerous  nodules  of  varying  size  up  to  a  marble. 
No  intestinal  adhesions  were  noted.  Wound  closed  after  hemorrhage  was 
stopped  by  packing.  Death  occurred  in  twenty-four  hours. 

Autopsy  by  Drs.  J.  L.  Glass  and  John  A.  Foote. 

Case.  Fairly  well-nourished  boy.  Abdomen  prominent.  Right  lung 
small  and  more  compressed  than  left.  Diaphragm  pushed  upward  to  level 
of  third  rib  on  right  by  liver.  Lungs,  kidneys,  and  spleen  normal. 

Liver,  weight  740  grams.  After  hardening  was  22  cm.  by  13  cm.  by  6 
cm.  It  was  mottled  red  in  color.  Superior  and  inferior  surfaces  were  covered 
by  about  seventy-five  nodules  varying  in  size  from  a  mustard  seed  to  a 
walnut.  Nodules  were  round,  confluent  in  some  areas,  and  were  lighter  in 
color  at  the  summit  of  each  boss.  Section  showed  these  nodules  throughout 
the  liver  substance.  When  cut  the  nodules  had  a  dark  center  with  a  capsule- 
like circle  of  lighter  tissue  outside. 

Microscopic  Examination.  Connective  tissue  of  interlobular  septa 
increased,  especially  near  the  bile  ducts.  Liver  cells  stain  irregularly,  show 
vacuoles  and  are  distorted  in  certain  areas.  Some  cells  have  unusually 
large  nuclei.  Compressed  liver  cells  and  fibrous  tissue  form  rings  in  areas 
corresponding  to  blood  vessels  with  atrophic  liver  cells  outside  these  rings. 
The  contents  of  these  nodules  are  red  blood  cells,  a  few  white  cells  and 
debris,  with  more  or  less  incomplete  lining  envelopes  of  large  endothelial 
cells  in  the  smaller  nodules,  sometimes  in  more  than  one  layer.  Outside  the 
endothelium  and  in  lacunae  in  the  fibrous  septa  corresponding  to  the 
wall  of  these  vessel  nodules  are  nests  of  cells,  some  of  which  resemble 
degenerated  liver  cells,  others  the  endothelial  lining.  These  endothelial 
cells  are  somewhat  rounded  with  very  large,  oval,  deeply  staining  nuclei, 
mitotic  figures  and  chromatin  showing  in  abundance.  In  observing  the 
smaller  vessels  they  are  found  to  be  literally  choked  with  endothelial 
cells,  double  and  triple  layers  of  cells  being  seen  in  some  fields.  These 
vessels  merge  into  masses  of  small  round  cells  in  the  connective  tissue 
trabeculae.  The  smaller  nodules  show  typical  tumor  formation  of  cells 
resembling  myxosarcoma,  a  sharp  line  of  demarcation  of  fibrous  tissue 
showing  between  these  areas  and  abnormal  liver  tissue  surrounding  them. 

Section  of  spleen,  lungs,  heart,  and  stomach  show  no  metastases. 


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HEMANGIOENDOTHELIOMA  OF  THE  LIVER      937 

Diagnosis.  Hemangioendotheliosarcoma. 

Veeder  and  Austin  (8)  in  their  report  of  the  first  American  case  of 
hemangioendothelioma  in  an  infant  in  19 12  could  find  only  three 
others  in  the  literature  at  that  time.  Stern  (9)  reported  a  typical  case 
in  19 1 5,  bringing  the  total  up  to  five.  To  this  should  be  added  in 
all  likelihood  the  cases  reported  as  sarcomas  by  Lendrop^  in  1893, 
de  Haan^  in  1903  and  Parker,^  as  well  as  the  one  just  reported 
by  the  writer.  A  case  rep)orted  by  Bondy*  in  191 1  as  angiosarcoma 
without  histological  details  was  similar  in  gross  anatomy  and  cHnical 
findings.  This  gives  in  all  nine  cases  of  enlargement  of  the  liver  in 
children  appearing  shortly  after  birth,  increasing  rapidly  about  the 
third  month,  with  no  jaundice,  little  disturbance  of  nutrition  and 
resulting  in  death  from  progressive  weakness  usually  about  the 
fifth  month.  The  liver  in  all  cases  is  enlarged  and  nodulated,  the 
nodules  made  up  of  dilated  blood  vessels.  A  proliferation  of  endothe- 
lium is  made  out  in  every  case  where  a  detailed  histological  study 
has  been  given.  The  case  of  Sawyer  (10)  abstracted  by  Veeder  and 
Austin  is  not  included  in  the  following  summary,  since  it  was  far 
from  typical  and  autopsy  revealed  other  conditions  which  may 
have  caused  death. 


Reported  by 


Clinical  History 


Gross  Anatomy 
OF  THE  Liver 


Histology 


Chervinsky. 

Arcb.  d.  Phys.  norm, 
et  path.  1885,  VI, 
553. 

Diagnosis,  endothe- 
lioma. 


Abdominal  _  enlarge- 
ment noticed  at  six 
weeks.  Growth 
very  rapid.  Death  at 
six  months  from 
general  exhaustion. 

No  jaundice. 


Weight,  943  grams. 
Very  large  liver. 
Purplish  red. 
Many  nodules  on 
surface  varying  in 
size  from  a  p)ea  to 
an  egg.  Nodules  on 
section  showed  a 
red  center  sur- 
rounded by  white 
rings,  some  showing 
fibrous  bands  run- 
ning to  the  periph- 
ery. 


Blood  spaces  lined 
with  endothelial 
cells  in  more  than 
one  layer  in  places, 
and  containing  red 
and  white  blood 
cells  and  debris. 
Capsule  about  nod- 
ule made  up  of 
compressed  cellular 
and  fibrous  tissue. 
Parts  of  liver  show 
fatty  degeneration 
in  filtration  and  an 
increase  of  perilobu- 
lar tissue. 


•  See  Summary  of  Malignant  Angiomas,  etc.,  p.  938. 

•  Ibid.,  p.  938. 

•  Ibid.,  p.  938. 
«  Ibid.,  p.  938. 


938      HEMANGIOENDOTHELIOMA  OF  THE  LIVER 


Reported  by 


Clinical  History 


Gross  Anatomy 
OF  THE  Liver 


Histology 


Bruchanow. 

Zeitscbr.  L  Heilk., 
1889,  XX,  431. 

Diagnosis,  endothe- 
lioma. 


Infant,  fifteen  weeks. 
Showed  angiomas 
of  the  skin  and  an 
abdominal  tumor. 
Death  from  exhaus- 
tion at  fifteen  weeks. 

No  jaundice. 


Weight,  710  grams. 
Dark  red  in  color, 
Nodulated.  _  Nod- 
ules vary  in  size 
from  pea  to  hen's 
egg.  On  section  are 
red  in  center  and 
whiter  at  periphery 
An  increase  of  in- 
terlobular tissue. 


Essentially  the  same 
as  Chervinsky's 
case. 


Lendrop. 
Hospitalstidende, 

1893,  p.  217. 
Diagnosis,  sarcoma. 


Infant,  female,  four 
months  old.  Large 
mass  in  abdomen. 

No  jaundice. 


Weight,  1625  grams 
Enormous  liver, 
nodular  and  dark 
red  in  color.  Nod 
ules  of  varying 
sizes  up  to  a  wal 
nut.  Section  shows 
nodules  throughout 
entire  liver. 


Nodules  contain 
round  cells  origi- 
nating in  endothe- 
lium of  interacinous 
blood  vessels  and 
penetrating  into  the 
veins.  Liver  cells 
compressed  and  de- 
generated. 


De  Haan. 

Ziegler's  Beitr.  z. 
Path.  Anat.,  1903, 
XXXIV,  Heft  2, 
215. 

Diagnosis,  sarcoma. 


Child  four  months 
old.  Large  nodular 
mass  made  out  in 
abdomen. 

No  jaundice. 


Weight,  867  grams. 
Liver  dark  and  cov- 
ered with  nodules 
of  all  sizes  showing 
lighter  under  a 
smooth  capsule, 
some  confluent. 
Section  shows  them 
throughout  liver. 


Nodules  contain 
many  round  cells 
with  deeply  stain- 
ing nuclei.  Blood- 
vessels dilated  and 
choked  with  large 
endothelial  cells. 
Tumor  masses  of 
similar  cells. 
Growth  due  to  pro- 
liferation of  capil- 
lary endothelium. 


Parker. 

Trans.    Path.    Soc., 

London,     XXXI, 

290. 
Diagnosis,  sarcoma. 


Infant  constipated, 
died  from  weakness 
aged  five  weeks. 
Abdominal  swelling 
noted  at  three 
weeks. 

No  jaundice. 


Lar^e  liver  nodulated 
with  millet  seed  to 
walnut-sized 
masses.  Contents 
whitish  at  edge, 
darker  at  center. 


Vessels  enlarged  and 
distended.  Liver 
shows  many  small 
round  cells,  especial- 
ly near  small  ves- 
sels. 


Bondy. 

Jm.  A.M.  A.,  1911, 

LVI,  12,  873. 
Diagnosis,  sarcoma. 


Increase  in  girth 
noticed  at  three 
weeks  due  to  mass 
in  liver  region. 
Exploratory  lapa- 
rotomy performed. 
Child  lived  to  three 
and  one-half 
months,  dying  from 
weakness.  No  au- 
topsy, but  portion 
of  liver  removed  at 
operation. 


Purplish  liver  seen  at 
operation  occupy- 
ing three-quarters 
of  abdominal  cav- 
ity. Surface  cov- 
ered with  nodules. 


No  histological  de- 
tails given.  A  diag- 
nosis of  angio-sar- 
coma  made  by 
pathologist. 


HEMANGIOENDOTHELIOMA  OF  THE  LIVER      939 


Reported  by 

Clinical  History 

Gross  Anatomy 
OF  THE  Liver 

Histology 

Veeder  and  Austin. 

Am.  Jm.  Med.  Sc, 
1912-13,  CXLIII, 
102-107. 

Diagnosis,  endothe- 
lioma. 

Female  child  showing 
enlargement  of  ab- 
domen   progressive 
since       birth. 
Brought  to  hospital 
at  ten  weeks.  Nod- 
ular mass   in   liver 
region.    Child  grew 
weaker,     dying     a 
week  later. 

Liver  enlarged  to  um- 
bilicus.   Many  red- 
dish purple  nodules 
varying      in      size 
from  a  millet  seed 
to  a  marble.       On 
section  show  a  red 
center  _  surrounded 
by  a  lighter  zone. 
These     are  ^  found 
throughout  liver. 

Nodules  made  of  di- 
lated vessels.  Blood 
spaces  packed  with 
red  cells.  Endothe- 
lium sometimes  in 
double  layers.  En- 
dothelial cells  have 
large  oval  nuclei. 
Around  each  nodule 
an  irregular  capsule 
of  connective  tissue 
and  compressed 
liver  cells.  Capsule 
of  Glisson  shows 
overgrowth  of  con- 
nective tissue. 
Liver  cells  show 
fatty  changes. 

Stem. 

Arcb.ofDiag.,191S, 
VIII,  72-73. 

Diagnosis,     heman- 
gioma. 

At  six  weeks  brought 
to  hospital  for  feed- 
ing advice.  Nodular 
liver    mass    noted, 
x-ray       showed 
tumor  extending  to 
pelvis. 

Child     left     hospital 
and  died  a  few  days 
later   of  weakness. 
Only  a  partial  ab- 
dominal     autopsy. 
Large   reddish-pur- 
ple nodular  liver. 

Portion  of  liver  re- 
moved showed  mul- 
tiple angiomatous 
cavities  lined  with 
many  endothelial 
cells. 

Foote. 
1918. 

Child  brought  to  hos- 
pital     at    three 
months  for  consti- 
pation.    Enlarge- 
ment   of   abdomen 
noted  and  a  nodular 
mass  made  out  in 
liver  region.       Op- 
eration showed  pur- 
plish nodular  liver. 
Considerable 
amount  of  bleeding 
from    cut    nodule. 
Child    died    within 
twenty-four  hours. 

Liver      weight,      740 
grams.         Covered 
with  nodules,  about 
seventy-five,   vary- 
ing in  size  from  a 
millet    seed    to    a 
walnut.         Section 
showed     nodules 
throughout      liver. 
Red    centers    with 
whiter    areas    sur- 
rounding them  seen 
in  each  nodule. 

Nodules  packed  with 
characteristic  cells, 
red  blood  cells,  and 
debris.  The  vessels 
show  lar^e  endothe- 
lial cells  in  multiple 
layers.  Vessel  and 
nodule  walls  thick- 
ened and  infiltrated 
with  large  round 
and  oval  nucleated 
cells.  Capsule  of 
Glisson  increased  in 
size  of  septa.  Capil- 
laries show  endo- 
thelial proliferation 
merging  in  places  to 
a  mass  of  primitive 
round  cells.  Mitotic 
figures    in     nuclei. 

In  spite  of  the  fact  that  no  metastases  can  be  demonstrated, 
the  malignancy  of  these  tumors  cannot  well  be  disputed.  Adami,  (i  i) 
after  defining  sarcoma  and  amplifying  his  definition,  says  in  italics. 

**Therefore  .  .  .  the  actively  growing  tumors  of  transitional  lepidic 
character  have  also  from  this  standpoint  to  be  included  as  sarcomatous." 


940      HEMANGIOENDOTHELIOMA  OF  THE  LIVER 

That  angiosarcoma  of  this  tj'pe  develops  from  within  the  vessel 
walls  by  endothelial  proliferation  is  urged  by  Dutton  (12)  in  his  report 
of  two  angiomas  of  the  skin  in  an  eight-year-old  child.  His  micro- 
photographs  show  the  same  endothelial  proliferation  and  histological 
pictures  seen  in  the  endothelial  tumor  of  the  liver  reported  by  the 
writer  and  others.  Fischer  (13)  has  collected  three  cases  of  hemangio- 
endothelioma of  the  liver  of  a  malignant  type  in  adults.  In  several 
beautiful  plates  he  shows  definitely  the  endothelial  proliferation 
and  infiltration  down  to  the  ultimate  typical  sarcoma  structure  of 
metamorphosed  endothelial  cells.  He  takes  issue  with  Ribbert  and 
maintains  that  these  tumors  develop  rapidly  by  successive  changes 
in  contiguous  apparently  normal  endothelial  cells.  "The  tumor 
cells  lie  in  normal  anatomical  relation  to  the  endothelial  tube,  prov- 
ing conclusively  that  the  cells  have  originated  in  this  location,  **  he 
says.  An  embryonic  type  of  liver  endothelium,  retaining  even  the 
embryonic  function  of  hematopoiesis  as  described  by  Borst,  Schwalbe, 
and  others,  is  responsible,  in  his  opinion,  for  the  rapid  and  peculiar 
growth  of  these  remarkable  tumors. 

Many  theories  have  been  put  forth  to  explain  the  origin  of  the 
simple  angiomas  and  the  hemangioendotheliomas  of  the  liver. 
Chervinsky,^  who  was  the  first  to  describe  hemangioendothelio- 
mas of  the  liver  in  an  infant,  believed  that  these  tumors  were  easily 
explained  through  the  theory  of  fetal  inclusion,  a  view  also  held 
by  Pilliet.  ( 1 4)  Bruchanow  ( 1 5)  believed  that  the  capillaries  of  the  liver 
established  an  abnormal  relationship  to  the  rest  of  the  liver,  es- 
pecially the  liver  cells,  continuing  their  growth  and  development 
independently  of  the  normal  relationships  of  adjacent  tissues.  To 
both  of  these  views  Schmieden  (16)  objected  that  a  simple  growth  or 
dilatation  of  vessels  of  the  type  described  was  no  true  blastoma 
formation,  such  angiomas  being  the  result  of  the  simple  growth 
and  dilatation  of  capillaries  into  budding  masses  of  liver  tissue 
which  in  the  process  of  development  had  been  cut  off  from  the  rest 
of  the  liver.  Ribbert  failed  to  inject  the  dilated  vessels  through  the 
hepatic  vein.  According  to  Mallory's  postulates,  in  true  hemangioen- 
dothelioma it  must  be  established  that  new  blood  vessels  are 
formed  and  that  the  endothelial  cells  have  proliferated. 

All  of  these  attempted  explanations  of  the  beginnings  of  these 
tumors  go  back  to  an  abnormal  developmental  condition  followed 

'  Chervinsky,  see  Summary  of  Malignant  Angiomas,  p.  937. 


HEMANGIOENDOTHELIOMA  OF  THE  LIVER      941 

by  an  unrestrained  growth  and  dilatation  of  the  blood  vessels.  How- 
ever, the  rapid  proliferation  of  the  endothehum  in  the  capillaries 
choking  them  and  extending  the  process  to  larger  vessels,  with 
the  resulting  stasis  and  dilatation  and  infiltration  of  the  vascular 
structure,  is  the  characteristic  picture  of  the  end  of  this  process, 
whatever  its  beginning  may  have  been.  The  primitive  type  of  cell 
seen  in  the  endothelium  of  vessels  with  large  nuclei  rich  in  chro- 
matin, showing  rapid  growth,  and  the  clinical  picture  of  rapidly 
growing  liver-tumor  without  jaundice,  accompanied  by  general 
weakness  and  terminating  fatally,  bear  out  to  an  unusual  degree 
Adami's  assertion  that  all  tumors  of  this  character  must  be  con- 
sidered as  sarcomas.  The  histological  evidence  in  the  cases  of  Dutton, 
Fischer,  and  the  writer  shows  that  these  growths  are  neither  true 
benign  hemangioendotheliomas  nor  typical  angiosarcomas,  but  a 
malignant  growth  originating  in  the  endothelium  of  the  blood 
vessels  forming  no  metastases,  perhaps  best  described  by  the  term 
bemangioendotbeliosarcoma  and  seen  characteristically  in  the  liver 
of  infants  during  the  first  few  months  of  life. 


BIBLIOGRAPHY 

1.  Staff  en.  A.,  "Die  malignen  Geschwulste  im  Kindesalter,"  Stuttgart,  1908. 

2.  Knott,  Van  B.,  Surg.,  Gynec.  &"  Obst.,  1908,  VII,  328-341. 

3.  KaufFmann,  Spezielle  patb.  Anat.,  1907,  579. 

4.  Michailow,  Arcb.  J.  Kinderb.,  1901,  XXI,  291. 

5.  Gatewood,  Tr.  Cbicago^Patb.  Soc,  VIII,  31 1-3 16. 

6.  Dutton,  J.  E.,  Liverpool  Med.-Cbir.  J.,  1898,  XVIII,  369-376. 

7.  Fischer,  B.,  Frankfurt.  Ztscbr.  J.  Patb.,  Wiesb.,  1913,  XII,  399-421. 

8.  Veeder  and  Austin,  Am.  J.  M.  Sc,  1912-13,  CXLIII,  pp.  102-107. 

9.  Stern,  A.,  Arcb.  Diagn.,  19 15,  VIII,  72-73. 

10.  Sawyer,  Rep.  Soc.  Study  Dis.  Cbild.,  Lond.,  1906,  VII,  19. 

11.  Adami,  "Principles  of  Pathology,"  1910,  I,  762. 

12.  Ibid.,  6. 

13.  Ibid.,  7. 

14.  Pilliet,  Progrks  Med.,  XXIX,  50. 

15.  Bruchanow,  Ztscbr.  J.  Heilk.,  1889,  XX,  431, 

16.  Schmieden,  Vircbow's  Arcb.f.  patb.  AruU.,  1900,  CLXL,  p.  373. 

17.  J.  Exper.  M.,  1908,  X,  575. 


THE  PRODUCTION  OF  AN  ANTIHEMOLYSIN    FOR 
THE  HEMOLYSIN  OF  BACTERIUM  WELCHII 

By  William  W.  Ford,  M.D., 

AND 

George  Huntington  Williams,  M.D. 

(From  the  Department  of  Bacteriology,  School  of  Hygiene  and  Public  Health,  Johns 

Hopkins  University) 

IT  has  previously  been  shown  by  Ford  and  Lawrence  that  the 
whey  from  market  milk,  which  decomposes  after  heating  to 
80°  C.  for  twenty  to  thirty  minutes,  contains  substances  which 
dissolve  the  red  blood  corpuscles  of  a  number  of  animals,  and  that 
these  substances  are  produced  in  the  milk  by  the  multiplication  of 
the  "gas  bacillus"  of  Welch  and  Nuttall.  The  hemolysin  of  this 
organism  has  been  further  shown  to  be  independent  of  the  acids 
produced  in  the  milk,  to  be  destroyed  at  about  60°  C,  to  be  precip- 
itable  by  ethyl  alcohol,  and  to  be  acted  upon  by  the  digestive 
ferments.  For  these  reasons  this  blood-taking  substance  was  placed 
in  the  group  of  bacterial  hemolysins,  and  the  destruction  of  blood 
by  cultures  of  the  gas  bacillus  was  attributed  to  its  activity,  and  not 
to  the  lactic  and  butyric  acids  which  are  produced  by  the  organism 
in  the  decomposition  of  the  ingredients  of  the  milk.  Subsequent 
investigation  of  the  properties  of  milk  cultures  of  the  gas  bacillus 
has  confirmed  our  earlier  observations  and  has  added  a  number  of 
other  points  of  interest,  especially  the  production  of  an  anti- 
hemolysin  to  this  substance. 

Preparation  oj  the  Hemolysin.  The  hemolysin  of  the  gas  bacillus 
can  be  obtained  from  milk  by  the  following  method.  Pure  cultures 
of  the  organism  are  isolated  from  market  milk  by  heating  flasks 
containing  about  300  c.c.  to  80°  C.  for  twenty  to  thirty  minutes  and 
incubating  at  37°  C.  In  the  majority  of  samples  so  treated  the 
"stormy  fermentation"  characteristic  of  this  species  appears  in 
twenty-four  to  forty-eight  hours.  Transfers  of  the  whey  from  such 
fermented  samples  to  litmus  milk  tubes  often  gives  pure  cultures 

942 


THE  PRODUCTION  OF  ANTI HEMOLYSIN 


943 


after  four  to  five  transfers,  owing  to  the  rapid  development  of 
Bacterium  Welcbiiy  by  virtue  of  which  it  overgrows  nearly  all  other 
micro-organisms  except  certain  acid-resistant  streptococci.  When 
the  cultures  do  not  become  pure,  the  material  may  be  run  through 
rabbits  by  the  usual  methods,  and  pure  cultures  obtained  from  the 
heart's  blood  or  liver.  With  such  freshly  isolated  strains,  large 
flasks  of  sterile  milk  containing  about  a  liter  are  inoculated  by 
pouring  into  them  the  entire  contents  of  a  twenty-four  hour  litmus 
milk  culture  of  the  organism,  about  12  to  15  c.c.  Such  flasks  of  milk 
undergo  violent  fermentation  within  twenty-four  to  forty-eight 
hours.  The  grosser  particles  of  curd  are  now  removed  by  filter 
paper  and  the  filtrate  immediately  neutralized  by  the  addition  of 
caustic  potash.  The  filtration  requires  eighteen  to  twenty  hours, 
during  which  time  there  is  a  further  multiplication  of  the  organisms, 
as  is  shown  by  an  increase  of  activity.  On  subsequent  neutralization 
an  abundant  gelatinous  precipitate  appears.  This  also  may  be 
removed  by  passing  through  filter  paper.  The  fluid  obtained  is 
clear,  rather  viscid,  yellowish  brown  in  color.  If  not  entirely  free 
from  bacteria  it  may  finally  be  run  through  a  Berkefeld  candle. 
This  final  product  of  the  milk  culture  of  the  gas  bacillus  has  marked 
hemolytic  properties,  as  shown  by  the  following  table: 

TABLE  I 


Hemolytic  Properties  of  Filtrate  from  Milk  Culture  of 
Tested  on  Rabbit's  Blood 

Bacterium  Welcbii 

Filtrate 

Red  Blood  Corpuscle 
5  Per  Cent 
Suspension 

Hemolysis 

1          c.c 

+ 

1  c.c. 

= 

Complete 

0 

75    c.c. 

+ 

1  c.c. 

= 

Complete 

0 

5      c.c 

+ 

Ic.c. 

= 

Complete 

0 

25    c.c 

+ 

1  c.c. 

= 

Complete 

0 

1      c.c 

+ 

1  c.c. 

= 

Complete 

0 

075  c.c 

+ 

1  c.c. 

= 

Complete 

0 

05    c.c 

+ 

1  c.c. 

= 

Complete 

0 

025  c.c 

+ 

Ic.c. 

= 

Complete 

0 

01    c.c 

+ 

1  c.c. 

= 

Negative 

1  c.c.  NaCl  0 

75    per 

cent  + 

1  c.c. 

= 

Negative 

From  this  table  it  may  be  seen  that  0.025  c.c.  of  the  filtrate 
suffices  to  bring  about  complete  solution  of  i  c.c.  of  a  5  per  cent 
suspension  of  rabbit's-blood  corpuscles,  representing  a  dilution  of 


944 


THE  PRODUCTION  OF  ANTIHEMOLYSIN 


1-40.  This  quantity  may  be  taken  as  the  hemolytic  unit  or  the 
hemolyzing  dose  of  the  filtrate.  Other  preparations  have  been 
obtained  in  which  the  hemolyzing  dose  is  somewhat  higher,  .01  c.c, 
but  they  are  exceptional.  The  usual  hemolytic  unit  is  about  0.25  c.c. 
in  a  freshly  prepared  filtrate  from  a  milk  culture  of  the  gas  bacillus. 
Preparation  of  an  Antibemolysin.  With  the  hemolytic  filtrates  as 
thus  prepared  a  series  of  rabbits  has  now  been  successfully  immun- 
ized. These  animals  were  under  treatment  for  some  months,  receiving 
gradually  increasing  doses  of  the  hemolysin.  During  the  treatment 
one  animal  developed  a  laboratory  paralysis;  while  another  became 
so  badly  infected  that  it  had  to  be  killed.  The  serum  of  the  other 
four  animals  contained  in  all  instances  substances  which  completely 
neutralized  the  hemolysin  of  the  gas  bacillus  in  high  dilution.  This  is 
shown  in  the  following  table: 

TABLE  II 

Strength  of  Antihemolysin  in  the  Serum  of  Rabbit  Immunized  with  the 
Hemolysin  of  Bacterium  Welcbii  Titrated  aganist  One  Hemolytic  Unit 
Represented  by  0.1  c.c.  of  the  Filtrate  Used 


Filtrate 

Serum 

Blood  Suspension 
5  Per  Cent 

Protection 

01  c.c. 

+ 

0 

1           C.C.                 + 

1  c.c.          = 

Complete 

01  c.c. 

+ 

0 

06      c.c.            + 

1  c.c. 

Complete 

01  c.c. 

+ 

0 

04      c.c.             4- 

1  c.c.           = 

Complete 

01  c.c. 

+ 

0 

02      c.c.             + 

1  c.c.           = 

Complete 

01  c.c. 

+ 

0 

01      c.c.             4- 

1  c.c. 

Complete 

01  c.c. 

4- 

0 

006    c.c.             + 

1  c.c.           == 

Complete 

0  1  c.c. 

+ 

0 

004    c.c.             + 

1  c.c. 

Complete 

01  c.c. 

+ 

0 

002    c.c.             + 

1  c.c. 

Complete 

01  c.c. 

+ 

0 

001    c.c.            4- 

1  c.c.           = 

Complete 

01  c.c. 

+ 

0 

0008  c.c.            + 

1  c.c.           = 

Complete 

01  c.c. 

+ 

0 

0006  c.c.             + 

1  c.c.           = 

Partial 

01  c.c. 

+ 

0 

0004  c.c.             4- 

1  c.c.           = 

Hemolysis 

01  c.c. 

+ 

0 

0002  c.c.             4- 

1  c.c.           = 

Hemolysis 

01  c.c. 

+ 

0 

0001  c.c.             4- 

1  c.c.           = 

Hemolysis 

Control 

+ 

1  C.C.  NaCIO.75% 

1  c.c.           =» 

Negative 

01  c.c. 

+ 

1  C.C.  NaClO.75%  • 

1  c.c,           = 

Hemolysis 

Complete  protection  against  one  hemolytic  unit  is  thus  afforded 
by  .0008  c.c.  of  the  serum,  or  a  dilution  of  1-1250.  Normal  serum 
prevents  hemolysis  only  when  used  in  large  quantities,  never  beyond 
a  dilution  of  i-io.  We  thus  have  an  artificial  or  an  immune  anti- 
hemolysin of  a  strength  far  beyond  that  of  the  antihemolysin  of  the 


THE  PRODUCTION  OF  ANTIHEMOLYSIN         945 

normal  serum.  The  usual  strength  of  the  immune  antihemolysin  was 
about  i-iooo. 

Conclusion.  By  the  immunization  of  animals  with  gradually 
increasing  doses  of  the  hemolysin  of  Bacterium  Welcbii  we  have  now 
produced  an  antihemolysin  of  a  strength  of  i-iooo  to  1-1280.  The 
production  of  this  substance  offers  the  final  proof  of  the  opinion 
previously  expressed,  and  definitely  places  the  hemolysin  of  the  gas 
bacillus  in  the  groups  of  bacterial  hemolysins  capable  of  acting  as 
antigens. 


I 


SYMPTOMLESS  OBLITERATION  OF  THE  SUPERIOR 

VENA  CAVA 

By  Thomas  B.  Futcher,  M.D.,  Baltimore,  Md. 

CASES  of  obstruction  of  the  superior  vena  cava  resulting  from 
compression  of  the  vein  from  without  by  an  aneurysm  or 
by  enlarged  glands,  whether  due  to  tuberculosis,  sarcoma,  or 
Hodgkin's  disease,  and  characterized  by  marked  dilatation  of  the 
superficial  thoracic  and  abdominal  veins,  with  the  venous  flow  from 
above  downwards,  are  comparatively  rare.  Still  more  uncommon 
are  those  cases  in  which  the  obstruction  is  believed  to  be  due  to 
atresia  of  the  lumen  of  the  superior  vena  cava  by  fibrous  tissue 
following  extension  of  a  mediastinitis  to  the  vein,  resulting  in  its 
partial  or  complete  obstruction.  The  following  case,  not  confirmed 
by  autopsy  unfortunately,  appeared  to  belong  to  the  latter  group. 
It  was  of  additional  interest,  owing  to  the  fact  that  the  patient 
appeared  to  have  no  symptoms  directly  referable  to  the  venous 
obstruction,  those  from  which  he  did  sufi'er  apparently  being  due  to 
the  myocardial  insufficiency  from  which  he  suff'ered. 

S.  M.,  Med.  No.  37,608,  colored,  male,  married,  age  forty-five  years, 
was  admitted  to  the  Johns  Hopkins  Hospital  on  March  21,  19 17,  hav- 
ing been  under  the  observation  of  Dr.  J.  Hall  Pleasants  and  the  writer  in 
the  Medical  Dispensary  since  March  13th.  His  complaint  was  shortness  of 
breath  and  weakness  of  the  heart. 

The  family  history  was  unimportant,  with  the  exception  that  his  wife 
had  had  two  miscarriages.  The  patient  had  mumps  at  ten  years  of  age 
and  measles  at  seventeen.  There  was  no  history  of  any  of  the  other  acute 
specific  fevers.  Between  the  ages  of  twelve  and  fifteen  he  had  several  mild 
attacks  of  arthritis,  however,  which  incapacitated  him  for  only  a  day  or 
two  at  a  time.  There  was  no  history  of  tonsillitis. 

He  performed  hard  manual  labor,  and  for  some  time  before  admission 
had  been  an  oyster-dredger  on  the  Chesapeake  Bay.  Although  for  the 
past  ten  years  he  had  experienced  some  palpitation  of  the  heart  on  exertion, 
he  had  been  able  to  perform  hard  labor  up  to  two  years  before  admission. 

946 


Photcxjraph  of  Patient,  Showing  Marked  Dilatation  of  the  Thoracic  and 
Abdominal  Veins,  the  Venous  Current  Being  from  above  Downwards. 


OBLITERATION  OF  SUPERIOR  VENA  CAVA       947 

No  history  of  any  venereal  infection  was  elicited,  notwithstanding  the 
subsequent  findings.  He  chewed  tobacco  moderately,  and  rarely  took 
alcohol  in  any  form.  His  greatest  weight  at  any  time  had  been  160  pounds. 

For  a  good  many  years,  at  least  ten  or  fifteen,  he  has  observed  enlarged 
veins  over  the  front  of  the  chest  and  abdomen.  He  had  never  experienced 
any  pain  over  the  upper  segment  of  the  chest. 

The  symptoms  for  which  the  patient  was  admitted  began  about  two 
years  previously.  The  onset  was  apparently  rather  abrupt,  with  a  sense  of 
weakness  and  dizziness  while  on  the  street,  and  he  was  taken  to  the 
Mercy  Hospital,  Baltimore,  from  the  authorities  of  which  the  following 
statement  was  obtained:  "Patient  found  unconscious  on  street  by  police 
and  brought  to  Mercy  Hospital,  March  23,  1915.  Diagnosis  at  that  time, 
myocarditis,  arrhjrthmia,  and  acute  dilatation  of  the  heart.  Patient  dis- 
charged April  I,  1915,  in  good  condition." 

The  patient  states  that  he  had  never  experienced  any  shortness  of 
breath  previous  to  this  attack.  The  day  of  the  attack  he  had  been  carrying 
bags  of  grain  which  he  thought  weighed  75  pounds  each.  While  he  never 
noticed  any  swelling  of  the  feet,  he  observed  shortly  after  this  attack  that 
his  face  would  be  swollen  after  a  night's  rest,  clearing  up  during  the  day. 

Following  his  first  admission  to  the  Mercy  Hospital  he  was  readmitted 
for  one  week  in  July,  19 15,  and  again  for  two  weeks  in  October,  191 5.  The 
symptoms  were  similar  to  those  in  the  first  attack.  From  October,  19 15, 
up  to  the  time  of  his  admission  to  the  Johns  Hopkins  Hospital,  the  patient 
had  not  been  able  to  perform  hard  labor,  owing  to  shortness  of  breath  and 
palpitation  of  the  heart,  although  he  had  not  been  confined  to  bed  for  any 
length  of  time.  He  had  not  complained  of  upper  thoracic  pain  and  had  had 
no  cough. 

Physical  Examination.  The  patient  was  a  well-nourished,  fairly 
muscular  colored  man,  weighing  147  pounds.  While  at  rest  there  was  no 
dyspnea.  On  baring  the  trunk,  the  outstanding  features  were  two  markedly 
dilated  venous  trunks  about  the  size  of  one's  index  finger,  extending  down 
each  side  of  the  sternum  and  anastamosing  with  the  superficial  epigastric 
veins  and  disappearing  at  the  level  of  Poupart's  ligament,  as  seen  in  the 
accompanying  photograph.  The  current  of  blood  was  from  above  down- 
wards. The  jugular  veins  were  considerably  distended,  as  were  those  also 
over  the  shoulders  and  upper  arms.  There  was  no  evident  cyanosis  nor 
any  definite  turgescence  of  the  face. 

The  examination  of  the  radials  showed  them  to  be  equal  on  the  two 
sides;  some  irregularity  from  "ventricular  premature  systole"  as  demon- 
strated in  the  Heart  Station  by  Dr.  M.  W.  Brown.  No  definite  thickening 
of  the  vessel  walls.  Pulse  rate  during  observation  was  between  72  and  130 


948       OBLITERATION  OF  SUPERIOR  VENA  CAVA 

per  minute.  The  blood  pressure  was  low,  the  systolic  ranging  between  94 
and  1 10  and  diastolic  between  72  and  85. 

The  pupils  were  equal.  Ophthalmoscopic  examination  showed  a 
little  tortuosity  of  the  retinal  arteries.  Veins  a  little  full.  Eyelids  a  trifle 
puff'y.  Conjunctivae  a  little  injected. 

The  lungs  were  clear  by  the  ordinary  methods  of  examination,  with 
the  exception  of  a  few  medium  moist  rales  at  the  bases. 

On  March  21,  191 7,  Dr.  Theodore  Janeway  made  the  following  note: 
**  Enlargement  of  sup>erficial  veins  over  lower  thorax  and  upper  abdomen. 
Blood  current  from  above  downwards.  Point  of  maximum  impulse  diff"use 
and  well  inside  the  mammillary  line.  The  relative  cardiac  dullness  extends 
12  cm.  to  the  left  in  the  fifth  interspace  and  8  cm.  to  the  right  at  the  level 
of  the  fourth  interspace.  Relative  mediastinal  dullness  reaches  2.5  cm.  to 
right  and  6  cm.  to  left  at  the  level  of  the  first  interspace.  No  definite  lift 
of  the  upper  sternum.  Presystolic  gallop  at  the  apex.  The  mitral  first 
sound  is  followed  by  a  loud,  rather  harsh  systolic  murmur  transmitted  to 
the  axilla,  but  not  widely  over  the  precordium.  It  is  heard  in  the  back 
below  the  angle  of  the  scapula.  Aortic  second  sound  is  not  snapping. 
Pulmonic  second  a  little  accentuated.  No  impulse  felt  in  episternal  notch. 
No  tracheal  tug. 

"Pupils  equal  and  react  to  light  and  accommodation.  Pulses  equal  and 
regular.  Vessel  walls  not  especially  thickened.  Liver  just  below  the  costal 
margin.  Spleen  not  palpable.  No  edema  of  legs.  Deep  reflexes  present,  but 
reduced. 

"Impression:  Myocardial  disease  with  relative  mitral  insufficiency. 
Probably  syphilis  of  the  aorta,  but  no  evidence  of  aneuryism.  Apparent 
obstruction  of  the  superior  vena  cava,  either  partial  or  above  azygos  vein." 

The  laryngoscopic  report  by  Dr.  Chisolm  was  as  follows:  "Cords 
approximate  fairly  well,  but  there  is  definite  weakness  of  the  right  cord, 
which  is  partially  compensated  by  over-adduction  of  the  left  cord." 

The  blood  Wassermann  reaction  was  quadruple  positive. 

The  complement  fixation  test  of  the  blood  was  positive  for  tuberculosis. 

The  report  on  the  roentgenogram  of  the  chest  was  as  follows: 
Dilated  heart  and  aorta.  Infiltration  of  both  lungs,  especially  the  right. 
Interlobular  pleurisy  on  both  sides.  Lung  condition  suggests  that  these 
changes  are  tuberculous. 

Fluoroscopic  report:  Dilated  aorta,  moderate  in  size.  The  pulsations 
are  quite  feeble.  The  heart  is  pulsating  very  slowly  and  there  are  pleural 
adhesions  in  right  lung.  Heart  is  enlarged. 

The  full  blood  count  revealed  nothing  worthy  of  comment. 

The  urine  showed  an  occasional  trace  of  albumin,  but  no  casts. 


I 


OBLITERATION  OF  SUPERIOR  VENA  CAVA       949 

The  temperature  was  practically  normal  throughout,  with  the  excep- 
tion of  a  slight  elevation  following  a  diarsenol  injection. 

The  therapy  consisted  of  rest  in  bed,  digitalis,  mercurial  inunctions, 
and  an  injection  of  0.2  mgm.  of  diarsenol. 

The  patient  was  discharged  on  April  19,  1917,  only  slightly  im- 
proved. He  insisted,  against  advice,  on  returning  to  his  work  as  an 
oyster-dredger,  but  with  instructions  to  return  to  the  Medical  Dispensary 
for  observation.  He  failed  to  do  so,  and  repeated  efforts  to  trace  the  patient 
have  been  unsuccessful,  so  that  it  is  impossible  to  report  the  subsequent 
history  of  the  case. 

This  patient  undoubtedly  had  obstruction  of  the  superior  vena 
cava,  and  a  considerable  part  of  the  blood  from  the  head  and  upper 
extremities  must  have  been  reaching  the  heart  by  way  of  the  in- 
ferior vena  cava,  through  the  enormously  dilated  superficial  thoracic 
and  abdominal  veins  in  which  the  flow  was  from  above  downwards. 
Without  knowing  whether  the  superior  vena  cava  was  obstructed 
below  or  at  the  level  of  the  entrance  of  the  vena  azygos  into  it,  it  is 
impossible  to  say  how  much  blood  might  be  reaching  the  heart 
through  the  latter  vein  by  means  of  its  communications  with  the 
internal  mammary  veins  by  way  of  the  intercostals. 

The  impression  was  that  the  symptoms  of  dyspnea  and  palpita- 
tion on  exertion  were  due  to  the  patient's  myocardial  insufficiency 
and  not  to  his  caval  obstruction.  The  patient  had  noticed  the  en- 
larged superficial  veins  for  ten  to  fifteen  years,  and  it  would  appear 
that  the  collateral  circulation  that  had  been  established  had  com- 
pletely compensated  for  the  caval  obstruction.  In  a  case  reported 
by  Vigoureux,  sixteen  years  elapsed  between  the  first  signs  of 
obstruction  and  death. 

As  this  patient  left  the  hospital  improved  from  his  myocardial 
insufficiency  symptoms,  and  as  the  case  did  not  come  to  autopsy, 
we  have  not  the  absolute  information  as  to  the  nature  and  situation 
of  the  obstruction  of  the  superior  vena  cava.  Although  the  roent- 
genograms of  the  chest  showed  some  diffuse  dilatation  of  the  arch 
of  the  aorta,  the  pulsation  was  feeble,  and  there  was  nothing  to 
indicate  pressure  on  the  superior  vena  cava  by  a  saccular  aneurysm. 
Further,  the  absence  of  a  tracheal  tug,  localized  pulsation  or  lifting 
at  the  level  of  the  sternum,  led  us  to  believe  confidently  that  an 
aneurysm  could  be  excluded.  The  absence  of  any  extensive  medias- 


950       OBLITERATION  OF  SUPERIOR  VENA  CAVA 

tinal  shadow  enabled  us  to  eliminate  a  mediastinal  tumor  as  the 
cause  of  pressure  on  the  superior  vena  cava.  By  exclusion,  we  were 
forced  to  conclude  that  the  caval  obstruction  was  due  to  a  medias- 
tinitis,  either  syphilitic  or  tuberculous  in  origin,  which  had  gradually 
involved  the  wall  of  the  superior  vena  cava,  possibly  also  causing  a 
local  thrombosis  of  the  vessel,  and  eventually  its  complete  atresia. 
The  chances  are  in  favor  of  there  having  been  a  syphilitic  medias- 
tinitis  originating  in  the  mediastinal  glands,  as  the  patient  had  a 
quadruple  positive  Wassermann.  The  possibility  of  the  caval  ob- 
struction having  been  due  to  a  tuberculous  mediastinitis  has  to  be 
entertained,  owing  to  the  fact  that  his  blood  gave  a  positive  comple- 
ment fixation  test  for  the  tubercle  bacillus,  and  also  from  the  fact 
that  the  roentgenograms  showed  nodules  in  both  lungs.  Clinically, 
however,  the  patient  had  no  signs  of  active  tuberculosis. 

That  obstruction  of  the  superior  vena  cava  evident  enough  to 
warrant  a  clinical  diagnosis  is  rare  is  indicated  by  the  fact  that  out 
of  41,346  medical  admissions  to  the  Johns  Hopkins  Hospital  up  to 
March  i,  19 19,  there  have  been  only  10  cases.  The  present  case, 
not  confirmed  by  autopsy,  and  the  remarkable  case  reported  by 
Osler,^  in  which  the  autopsy  showed  complete  atresia  of  the  superior 
vena  cava  and  the  innominate  vein,  secondary  to  a  fibrous  medias- 
tinitis probably  tuberculous  in  origin,  were  the  only  2  in  which  the 
vein  was  thought  to  be  obstructed  as  a  result  of  the  extension  of  an 
inflammatory  process  from  a  chronic  mediastinitis.  Of  the  remaining 
8,  4  were  due  to  compression  of  the  vein  by  an  aneurysm,  i  by  en- 
larged glands  due  to  Hodgkin's  disease,  and  3  by  mediastinal  tumors. 

Up  to  1903  Osier  had  collected  from  the  literature  29  cases  of 
complete  obstruction  of  the  superior  vena  cava.  Space  will  permit 
only  a  brief  reference  to  the  cases  reported  in  the  literature  since  that 
date.  Search  of  the  Index  Medicus  reveals  only  1 1  references  to 
obliteration  or  obstruction  of  the  superior  vena  cava  since  1903. 
In  only  3  was  there  a  fibrous  obstruction  of  the  vein.  One  of  these, 
reported  by  A.  Meyer,  was  congenital  in  origin,  and  both  venae 
cavse  were  obliterated.  This  seems  to  be  the  only  congenital  case  on 
record.  The  other  2  cases  were  reported  by  Comby,  Vigoureux, 
and  Collet,  and  A.  M.  Gossage.  In  the  remaining  8  the  obstruction 
was  occasioned  by  pressure  from  without  by  an  aneurysm  or  a  tumor. 

*  Johns  Hopkins  Hosp.  Bull.,  1903,  XIV,  169. 


THE  STUDY  OF  MORBID  ANATOMY 
By  Alexander  G.  Gibson,  D.M.  (Oxon),  F.R.CP.  (Lond.) 

Lecturer  in  Morbid  Anatomy  in  the  University  of  Oxford 

IT  is  desirable,  from  time  to  time,  to  take  stock  of  the  various 
ancillary  subjects  in  relation  to  medicine,  for  the  advancement 
of  knowledge  in  neighbouring  sciences  and  in  special  branches  of 
medicine  render  previous  notions  of  such  relations  obsolete;  and  un- 
less the  links  are  occasionally  renewed  our  faith  in  the  subject  itself 
is  liable  to  wane.  This  paper  essays  to  review  the  special  functions  of 
morbid  anatomy  as  a  branch  of  pathology  in  relation  to  clinical 
medicine. 

Morbid  anatomy,  studied  with  a  broad  outlook  on  disease  and 
with  the  best  methods  of  technique,  is  still  the  basis  of  teaching 
in  clinical  medicine,  and  one  of  the  main  opportunities  for  advance 
in  knowledge.  It  is  the  means  whereby  pathological  processes  can 
be  displayed  in  the  clearest  way  and  rendered  useful  both  as  a  means 
of  ascertaining  their  causation  in  individual  patients  and  in  order 
to  reveal  new  causes  and  processes. 

What  is  wanted  is  a  return  to  the  Hunterian  outlook,  a  scheme 
in  which  all  anatomical  manifestations  are  used  as  stepping  stones 
to  the  elucidation  of  disease.  There  is  some  danger,  in  the  inevitable 
tendency  to  speciaHsation,  to  divorce  morbid  anatomy  from  clinical 
medicine.  Necessarily  there  must  be  men  who  make  it  their  sole 
study,  men  who  spend  their  lives  on  the  science  itself,  and  who  have 
no  concern  with  practice.  But  wherever  such  men  be,  they  should  be 
in  the  closest  touch  with  the  clinicians  and  the  clinical  work  of  the 
hospitals  they  serve;  they  should  be  willing  so  to  utilise  their  re- 
sources that  the  main  purpose  of  medicine,  the  discovery  and  cure  of 
disease,  is  facilitated  and  explored.  From  the  clinical  standpoint 
again,  there  must  be  a  desire  to  utilise  everything  that  may  be  estab- 
lished by  the  morbid  anatomist  for  the  benefit  of  the  patient;  there 
should  be  no  such  term  as  "pure  clinician." 

Formerly  a  good  deal  of  what  passed  for  pathology  was  of  the 
"arm-chair"  variety;  a  return  of  the  Hunterian  outlook  would  rid 
us  of  views  that  are  insufficiently  tested  by  either  observation  or 

951 


952  THE  STUDY  OF  MORBID  ANATOMY 

experiment.  The  soundest  of  the  older  physicians  looked  upon  mor- 
bid anatomy  as  the  centre  point  of  all  pathology,  and  notwithstand- 
ing the  claims  of  bacteriological  and  experimental  investigations  this 
view  is  at  the  present  time  amply  justified. 

The  amount  of  pathological  learning  demanded  from  students 
varies  considerably  in  different  universities  and  examining  bodies. 
Though  full  courses  are  given,  an  adequate  standard  of  knowledge 
is  not  always  insisted  upon  even  in  those  examinations  that  appear 
to  require  most  training.  Many  physicians  of  the  previous  genera- 
tion have  acquired  a  knowledge  of  pathology  only  by  careful 
reading  and  post-mortem  observation  during  the  practice  of  their 
profession.  It  must  also  be  admitted  that  for  the  bulk  of  prac- 
titioners, pathological  reasoning  appHed  to  clinical  medicine  is 
faulty.  Few  practitioners,  however,  can  avoid  having  some  system 
of  pathology  that  will  explain  clinical  events  both  to  themselves 
and  to  their  patients.  The  mental  isolation  and  absence  of  patho- 
logical facilities  in  many  types  of  practice  tend  to  develop  in  each 
practitioner  so  situated  a  system  of  reasoning  which  often  bears 
the  flimsiest  relation  to  facts.  Teachers  of  morbid  anatomy  ought 
to  set  themselves  to  put  into  the  student  the  sound  principles  of 
pathology  which  can  always  be  demonstrated  post-mortem  and  to 
refuse  to  countenance  any  hypotheses  which  are  not  based  on  such 
objective  data.  Such  expressions  as  rheumatism,  indigestion,  neu- 
ralgia, would  not  imply  a  final  diagnosis,  but  only  a  symptom  of 
the  physical  condition  which  underlies  it.  Those  who  use  these 
terms  improperly  are  the  victims  of  a  system  which  does  not  provide 
an  efficient  pathological  training,  and  they  p>oint  the  way  to  a  more 
thorough  training  of  the  future  student.  The  teaching  of  morbid 
anatomy  should  give  him  a  philosophy  that  he  can  apply  with  bene- 
fit to  his  patients,  and  upon  which  he  can  subsequently  build. 

A  widening  of  the  scope  and  an  increase  of  the  pathological 
training  is  a  matter  of  importance  in  the  present  training  of  students. 
It  may  be  objected  that  the  curriculum  is  already  overburdened  and 
that  further  loading  of  it  would  only  defeat  the  purpose  in  view. 
But  we  must  not  fail  to  adjust  our  methods  to  modern  conditions. 
The  medical  students  of  one  hundred  years  ago  were  taught  as  ap- 
prentices by  daily  contact  in  their  earliest  days  of  studentship  with 
the  manifold  expressions  of  disease  in  the  patient.  Throughout  the 


THE  STUDY  OF  MORBID  ANATOMY  953 

whole  of  their  career  they  never  lost  touch  with  patients.  Then 
came  the  introduction  of  the  anatomical  studies,  later  followed  by 
chemistry,  physics,  biology, and  physiology;  and  now  in  some  uni- 
versities we  have  an  intermediate  year  devoted  to  pathology, 
pharmacology,  and  elementary  physical  diagnosis  before  the  real 
hospital  work  begins.  The  special  study  of  pathology  as  an  intro- 
duction to  medicine  and  surgery  ought  to  be  looked  upon  as  a  means 
of  preparing  the  mind  of  the  student  to  take  more  advantage  of  the 
years  in  the  wards,  so  that  when  fully  equipped  for  practice,  he  can 
interpret  correctly  the  multitudinous  phases  of  disease  he  has  not 
seen  while  in  hospital.  It  cannot  be  said  that  modern  practitioners 
are  any  less  skilled  than  those  of  former  generations,  notwith- 
standing the  fact  that  their  contact  with  patients  during  their  years 
of  training  is  actually  less  than  formerly. 

The  subjects,  apart  from  the  fundamental  ones  of  anatomy  and 
physiology,  that  should  form  the  immediate  basis  of  clinical  medi- 
cine are  morbid  anatomy,  bacteriology,  and  experimental  medicine, 
and  of  these  the  first  is  by  far  the  most  essential  in  training  the  mind 
to  solve  the  problems  of  disease.  The  reason  for  this  is  that  the 
greater  bulk  of  diseased  processes  which  the  practitioner  meets 
are  gross,  inflammations,  local  and  general,  vascular  lesions,  degener- 
ative processes;  all  such  as  produce  physical  signs  either  at  the  site 
of  or  away  from  the  lesion,  and  morbid  anatomy  is  the  only  subject 
that  will  teach  a  student  to  think  rightly  in  the  terms  of  these 
processes.  Wisdom  in  clinical  medicine  may  be  acquired  by  bedside 
study  exclusively,  but  a  lifetime  spent  in  this  way  will  fail  to  win 
the  same  skill  of  one  helped  by  appropriate  anatomical  study  of 
disease.  That  this  is  recognised  by  physicians  who  have  the  opp)or- 
tunity  is  proved  by  the  fact  that  some  of  the  best  morbid  anatomists 
are  primarily  physicians.  On  the  other  hand,  some  highly  skilled 
physicians  are  ignorant  of  some  anatomical  processes;  in  the  text- 
book of  an  eminent  physician  is  a  paragraph  which  indicates  a 
failure  to  appreciate  the  fact  that  infarcts  of  the  lung  occur  in  cardiac 
disease,  though  he  is  aware  of  the  symptoms  in  the  patient  and  the 
anatomical  appearances  after  death  he  fails  to  recognise  the  process. 
Properly  conducted  courses  of  morbid  anatomy  in  the  years  of 
medical  training  should  completely  do  away  with  such  mistakes  in 
the  elements  of  pathology. 


954  THE  STUDY  OF  MORBID  ANATOMY 

To  picture  to  himself  the  anatomical  lesions  that  underlie  symp- 
toms should  be  the  habit  of  every  practising  doctor.  He  should  be 
able  to  penetrate  sufficiently  deeply  into  the  problems  of  disease 
as  not  to  be  satisfied  with  a  diagnosis  which  merely  connotes  a 
symptom,  as:  congestion,  bronchitis,  indigestion,  which  imply 
nothing  more  than  items  in  particular  diseased  conditions.  To  take 
only  one  of  these  terms,  bronchitis,  to  the  average  practitioner 
means  rhonchi  heard  on  auscultation  of  the  chest.  The  greater 
number  of  these  cases  are  the  result  of  an  infection  of  the  bronchial 
tubes,  and  rightly  described  as  bronchitis,  but  it  also  occurs  as  an 
item  in  a  number  of  other  conditions,  e.g.,  stasis  in  the  lung  vessels — 
increased  secretion  as  in  tetanus  and  uraemia,  or  as  the  result  of 
mahgnant  metastases  of  the  lung.  The  term  septic  pneumonia  again 
is  a  loose  clinical  term  with  no  proper  counterpart  as  a  pathological 
process;  it  usually  means  a  pneumonic  process  in  the  course  of  a 
septicaemia  which  is  frequently  a  septic  pulmonary  embolism. 
Further,  the  term  sapraemia  does  not  correspond  to  any  pathological 
condition  known.  In  its  anatomical  features  it  is  indistinguishable 
from  mild  septicaemia.  In  one  of  his  addresses  Sir  William  Osier 
has  insisted  on  this,  the  anatomical  view  of  the  disease,  in  order  to 
guard  against  the  tendency  to  think  that  the  patient  who  is  the 
subject  of  a  definite  anatomical  disease  should  ever  be  looked 
upon  as  if  that  disease  did  not  exist. 

The  diagnosis  of  clinicians  is  in  some  diseases  more  accurate 
than  is  possible  to  mere  naked-eye  anatomy.  On  more  than  one 
occasion  I  have  examined  a  uterus  removed  for  carcinoma  in 
which  the  diagnosis  could  not  be  confirmed  with  the  naked  eye, 
and  yet  histologically  the  diagnosis  was  upheld.  Again  a  clinical 
diagnosis  of  carcinoma  of  the  stomach  was  reversed  to  tubercular 
peritonitis  at  the  post-mortem  examination,  but  confirmed  on  the 
histological  examination.  The  chnician  deals  with  the  complaints  of 
patients  which  in  some  cases  form  extraordinarily  delicate  expres- 
sions of  deranged  function.  This  is  specially  noticed  in  the  diagnosis 
of  lesions  in  the  central  nervous  system  by  the  neurologist. 

It  is  these  considerations  that  force  one  to  the  conclusion  that 
morbid  anatomy  during  the  student  years  is  not  studied  with  suffi- 
cient thoroughness  and  determination.  On  the  average,  the  student 
spends  two  years  studying  mainly  anatomy  and  physiology.  In  its 


THE  STUDY  OF  MORBID  ANATOMY  955 

bearing  on  medicine  and  surgery  pathological  anatomy  should 
occupy  no  less  important  place.  What  is  required  is,  first,  a  recognition 
of  its  value,  secondly,  a  reorganisation  and  an  energetic  prosecution 
of  class  work  and  demonstrations  making  it  more  of  a  principal 
than  a  subsidiary  subject  that  in  the  minds  of  the  student  it  has  a 
tendency  to  become.  If,  however,  morbid  anatomy  is  to  find  its 
proper  place  in  the  medical  study,  not  only  must  it  explain  the 
problems  of  the  bedside,  but  it  must  constantly  receive  inspiration 
and  help  from  clinical  medicine.  The  morbid  anatomist  has  fre- 
quently to  lay  bare  the  mistakes  of  a  clinician  in  the  post-mortem 
room,  and  this  must  never  engender  a  self-sufficing  attitude  towards 
these  problems  as  they  appear  in  the  wards,  problems  in  which  the 
most  highly  skilled  are  liable  to  error.  It  is  necessary  for  the  morbid 
anatomist  occasionally  to  test  his  results  by  clinical  methods. 
For  instance,  it  is  impossible  to  say  of  certain  tumours  of  the  breast 
whether  they  are  malignant  or  not;  this  especially  applies  to  tumours 
removed  by  the  surgeon  either  wholly  or  in  part  and  for  which  a 
diagnosis  is  asked.  The  only  criterion  that  can  guide  the  pathologist 
to  an  opinion  is  the  amount  and  the  degree  of  the  hypertrophic 
process  evident  under  the  microscope.  On  this  point  the  opinion 
formed  from  fixed  preparations  can  never  be  final;  the  real  test  is 
the  absence  of  recurrence  in  the  body  of  the  patient  whose  history 
would  reveal  the  success  or  failure  of  the  surgeon. 

Morbid  anatomical  diagnosis  should  always  if  possible  be  setio- 
logical;  it  is  no  help  to  the  clinician  to  be  told  that  there  is  fibrosis, 
necrosis,  round-celled  infiltration,  and  such  like  phenomena,  unless 
those  are  preliminary  to  the  expression  of  an  opinion  on  the  nature 
and  if  possible  the  cause  of  the  tissue  condition.  Many  lesions  met 
with  clinically  cannot  be  fully  explained  by  even  the  most  searching 
anatomical  investigation.  Take,  for  instance,  the  granulomata — 
those  formed  by  known  organisms  such  as  tubercle  bacilli  and  the 
Spirochete  pallida  can  usually  be  reported  on  clearly  enough,  but 
when  one  comes  to  deal  with  the  healing  lesion  or  a  scar  showing 
none  of  the  features  of  the  known  granulomata,  no  proper  setio- 
logical  diagnosis  can  be  given;  the  problem  then  may  be  clinically 
soluble  by  an  enquiry  into  the  previous  history  of  the  patient  guided 
by  such  suggestions  as  may  appear  probable  from  the  anatomical  apn 
pearances.  Gummata  in  the  healing  stages  are  notoriously  difficult. 


956  THE  STUDY  OF  MORBID  ANATOMY 

and  should  always  be  confirmed  either  by  a  search  for  spirochaetes, 
or  a  Wassermann  reaction,  or  by  both.  Sarcomata,  again,  are  often 
mistaken  even  by  fairly  skilled  workers;  especially  are  they  difficult 
in  lymphatic  tissues. 

Let  us  now  turn  to  another  aspect  of  morbid  anatomy,  namely, 
the  part  it  may  be  expected  to  play  in  the  advancement  of  knowl- 
edge. The  subject  may  be  looked  upon  as  a  branch  of  anatomy,  a 
science  mainly  descriptive  and  a  part  of  that  great  group  of  sciences 
dealing  with  observation  which  may  be  termed  natural  history. 
Though  the  main  naked-eye  features  of  most  disease  processes 
are  known  and  have  been  described,  it  cannot  be  said  that  they 
have  been  fully  worked  out;  least  of  all  can  it  be  said  to  be  so  in 
respect  of  their  histology.  When  it  is  recognised  that  the  chemical 
processes  in  the  normal  cell  as  revealed  by  special  histological 
technique  are  known  only  in  the  most  fragmentary  manner,  it 
applies  much  more  strongly  to  diseased  tissues.  The  fact  is  the 
morbid  anatomist  has  the  power,  subject  to  the  limitations  of  the 
microscope  and  the  technique  employed,  to  see  right  into  the  centre 
and  origin  of  the  diseased  processes.  An  important  item  in  the  proof 
of  the  cause  of  an  infective  process  being  due  to  a  particular  organism 
lies  in  the  discovery  by  the  microscope  of  the  organisms  in  the  site 
of  the  lesions,  e.g.,  tubercle  bacilli,  and  Spirocbaete  pallida.  In  this 
respect  morbid  anatomy  and  bacteriology  must  go  hand  in  hand, 
the  first  controlling  the  findings  of  the  second.  Morbid  anatomical 
investigations,  indeed,  require  constant  confirmation  and  control  by 
bacteriological  and  experimental  methods.  Morbid  anatomy  with- 
out bacteriological  and  experimental  controls  reverts  to  a  purely 
anatomical  and  descriptive  science.  On  the  other  hand,  bacteriology, 
if  applied  to  medicine  without  the  controlling  guidance  of  morbid 
anatomy,  tends  to  become  botanical.  When  these  subjects  can  be 
prosecuted  in  sympathy,  the  one  acts  as  a  stimulant  to  the  other. 

An  aspect  of  morbid  anatomy  which  offers  ample  scope  for  in- 
vestigation in  conjunction  with  clinical  work  is  the  eflPect  in  the 
living  of  lesions  of  organs  and  particular  parts  of  organs.  Much 
progress  has  already  been  made,  as,  for  instance,  in  the  manifestation 
of  lesions  of  the  suprarenal,  thyroid,  and  of  such  viscera  as  are  liable 
to  destructive  phenomena.  Such  investigation  has  been  perfected 
in  a  high  degree  in  the  central  nervous  system,  but  with  some  notable 


THE  STUDY  OF  MORBID  ANATOMY  957 

exceptions  the  same  can  hardly  be  said  of  lesions  of  the  cardio- 
vascular system;  despite  all  the  energy  that  has  been  spent  upon  it, 
we  have  still  to  seek  for  anatomical  evidence  in  certain  cases  of 
cardiac  failure.  The  right  method  for  such  cases  is  that  pursued  by 
Mackenzie,  who,  after  observing  clinical  symptoms  in  his  patients 
for  prolonged  periods  with  the  accuracy  of  a  skilled  observer,  en- 
deavoured to  elucidate  these  symptoms  in  the  light  of  the  anatomical 
appearances  after  death.  These  are  problems  in  which  the  general 
practitioner  can  do  most  useful  work  if  he  is  given  the  opportunity 
by  being  associated  with  an  active  department  of  morbid  anatomy. 
An  intelligent  patient  suffering  from  an  obscure  and  doubtful  disease, 
and  in  sympathy  with  his  doctor,  seldom  fails  to  appreciate  the  diffi- 
culties of  medical  practice.  These  are  the  cases  which,  if  carefully 
recorded  during  hfe,  and  examined  post-mortem,  will  of  a  certainty 
add  to  the  knowledge  of  medicine.  The  consent  of  many  such 
patients  can  be  obtained  readily  enough  to  a  post-mortem  exam- 
ination. If  this  method  were  pursued  as  opportunity  oflFered,  the  ac- 
curacy of  clinical  methods  would  be  enhanced  and  the  science 
of  medicine  would  be  subject  to  a  constant  revision. 

It  may  confidently  be  hoped  that  as  the  disturbing  conditions 
aroused  by  the  war  settle  down,  research  will  be  stimulated,  and 
teaching  in  medicine  will  be  subject  to  revision.  Though  morbid 
anatomy  deals  with  the  dead,  there  is  no  reason  why  in  both  respects 
of  research  and  teaching  it  should  not  be  made  a  living  subject. 
One  aspect  of  it  deals  undoubtedly  with  dry  bones  and  pickled 
specimens  in  bottles,  but  the  processes  which  these  specimens  reveal 
are  those  in  the  living  bodies  of  patients  in  the  wards  to  which  they 
can  constantly  be  referred.  Some  experience  in  the  teaching  of 
students  on  these  lines  has  convinced  me  that  it  is  the  right  and 
only  method.  The  keenness  or  apathy  of  the  student  ought  to  be  a 
guide  to  the  teacher  of  the  real  value  of  his  teaching,  and  under 
this  method  when  morbid  anatomy  consists  not  in  the  identification 
of  lesions  of  dead  specimens,  but  in  the  recognition  of  a  process  which 
can  be  identified  in  the  living,  his  keenness  shows  no  tendency  to 
wane.  It  is  these  thoughts  that  stimulate  the  main  plea  of  this  paper 
for  a  full  recognition  of  the  value  of  morbid  anatomical  teaching, 
and  for  a  thorough  reorganisation  of  departments  of  morbid  anatomy 
in  relation  to  schools  of  medicine. 


LEUCOCYTES  AND  PROTOZOA 
By  E.  S.  Goodrich  and  H.  L.  M.  Pixell  Goodrich,  Oxford 

INSTANCES  of  Protozoa  known  to  be  destroyed  by  leucocytes 
are  decidedly  rare,  whereas,  in  animals  infected  with  bacteria 
one  may  expect  to  find  some  phagocytosis  taking  place,  how- 
ever susceptible  the  host  may  be.  Bacteria  taken  up  by  leucocytes 
never  multiply,  and  generally  degenerate  rapidly,  although  they  may 
retain  their  virulence  for  a  time,  even  occasionally  surviving  their 
host  cells.  However,  they  have  not  the  power  possessed  by  protozoa, 
such  as  Leishmania,  Toxoplasma,  certain  Leucocytozoa  and  Haemo- 
gregarines,  of  adapting  themselves  to  passing  through  important 
stages  of  their  life-history  in  such  positions.  Some  of  these  protozoa 
seek  out  phagocytes  as  their  host  cells,  wherein  they  multiply,  and 
soon  cause  degenerative  changes,  first  made  apparent  by  a  necrosis 
of  the  nuclei.  Many  other  protozoa  live  free  in  the  fluids  of  the  body 
immune  under  ordinary  circumstances  to  the  attack  of  leucocytes.^ 
Among  blood  parasites  are  the  well-known  Trypanosomes  and  Try- 
panoplasms,  also  certain  intestinal  flagellates  such  as  Giardia, 
Trichomonas,  Trichomastix  (8)  and  Leptomonas  (28),  sometimes 
found  in  the  blood  of  reptiles.  These  intestinal  flagellates  are  perhaps 
the  most  striking  examples,  for  since  they  cannot  be  regarded  as  true 
blood  parasites,  one  would  expect  them  to  be  rapidly  destroyed.  Other 
protozoa,  such  as  many  Coccidia  and  Myxosporidia,  live  in  the  tis- 
sues of  the  body,  especially  in  the  connective  tissues  and  muscles. 
These  parasites,  though  for  the  most  part  motionless  and  constantly 
exposed  to  wandering  phagocytes,  are  not  known  to  be  interfered 
with  by  them.  Not  only  may  leucocytes  serve  as  hosts  to  certain  pro- 
tozoa, they  may  even  be  used  as  food  by  some  parasitic  amoebae. 
Entamoeba  gingivalis  devours  leucocytes,  especially  the  small  mono- 
nuclear corpuscles  or  lymphocytes  brought  to  the  site  of  pyorrhoea 

^  In  speaking  of  leucocytes,  it  is  understood  that  we  mean  leucocytes  in  general,  not 
necessarily  the  haemic  ones,  which  have  been  proved  to  be  only  wandering  through  the  blood 
as  through  tissues  in  general. 

958 


LEUCOCYTES  AND  PROTOZOA        959 

lesions,  and  these  corpuscles  may  be  seen  in  various  stages  of  di- 
gestion, Fig.  I.  The  favourite  habitat  of  this  parasite  is  just  below 
the  tartar  ridge,  where  it  is  surrounded  by  abundance  of  leucocytes 
in  the  issuing  pus  (39).  It  has  also  been  stated  that  Entamceba  histoly- 
tica sometimes  engulfs  leucocytes  (3)  as  well  as  the  more  usual 
haematids. 

It  is  impossible  to  attribute  this  impotence  of  leucocytes  in  the 
presence  of  protozoa  to  the  size  of  the  parasites,  for  we  know  that 
some  Microsporidia,  e.g.,  Thelohania,  are  smaller  than  certain  bac- 
teria and  much  smaller  than  many  foreign  particles  which  are 
readily  phagocyted.  Also,  it  is  known  how  eflPectually  the  leucocytes 
of  some  Invertebrates  can  deal  co-operatively  with  relatively  huge 
Gregarines  (see  below).  However,  as  far  as  Vertebrates  are  con- 
cerned, among  the  very  few  protozoa  which  have  been  shown  to  be 
devoured  by  the  phagocytes  of  a  susceptible  animal  are  the  malarial 
parasites  (Haemamoebse).  Even  here  there  is  difference  of  opinion  as 
to  the  extent  to  which  the  phagocyte  is  an  active  enemy  of  the 
haemamoebae,  and  few  pathologists  can  be  found  now  to  support 
Metchnikoff's  opinion  that  to  phagocytes  alone  we  owe  spontaneous 
recovery  in  malaria. 

Not  long  after  the  discovery  of  the  specific  parasites  of  this 
disease  by  Laveran  (24,  1880),  Marchiafava,  Celli,  and  Guarnieri 
are  stated  (30,  p.  174)  to  have  studied  "the  phenomena  of  their 
phagocytosis  directly  under  the  microscope  in  blood  as  it  circulates." 
In  addition,  Golgi,  Metchnikoff,  Bignami,  Osier,  and  other  pioneer 
workers  on  malaria  describe  the  process  as  taking  place  in  the  blood 
or  organs,  especially  the  spleen  and  liver.  Just  previous  to  schi- 
zogony a  haemamoeba,  for  instance  Plasmodium  vivax  of  tertian 
malaria,  almost  completely  fills  the  infected  haematid,  which  then 
bursts,  setting  free  a  large  amount  of  melanin  and  the  young  mero- 
zoites.  The  latter  invade  other  corpuscles,  and  as  a  rule  repeat  this 
non-sexual  cycle.  As  the  setting  free  of  a  new  generation  of  mero- 
zoites  is  known  to  synchronise  with  an  attack  of  fever,  and  phagocy- 
tosis has  been  demonstrated  to  be  most  marked  in  the  early  hours 
of  the  pyrexial  period — one  would  expect  the  haemamcebae  devoured 
to  be  chiefly  these  minute  forms  without  pigment.  However,  al- 
though parasites  have  been  said  to  be  ingested,  we  can  find  no 
mention  of  this  particular  stage.  Of  course  dead  and  dj'ing  parasites 


g6o  LEUCOCYTES  AND  PROTOZOA 

and  cells  as  well  as  the  melanin  freed  from  them  are  rapidly  seized; 
but  this  is  no  proof  of  the  phagocytosis  of  living  parasites.  The 
presence  of  melanin  in  circulating  corpuscles  is  one  of  the  chief 
characteristics  in  the  diagnosis  of  malaria,  and  was  described  even 
before  the  parasite  was  discovered. 

Unfortunately  observations  as  to  phagocytosis  of  malarial  par- 
asites in  lower  animals  are  not  nearly  so  complete  as  they  should 
be — so  many  observers  have  been  content  to  record  the  presence  of 
haematozoa  without  studying  their  behaviour  and  fate  in  the  organs 
of  the  body.  Now  since  the  tissues  of  such  animals  can  be  examined 
perfectl}'^  fresh  at  any  stage  of  infection,  interesting  results  should 
be  obtained  free  from  possibility  of  error. 

Berenberg-Gossler,  (i)  after  careful  investigation  of  Plasmo- 
dium kocbi  and  P.  brasilianum  in  monkeys,  states  that  he  cannot 
confirm  the  generally  accepted  occurrence  of  phagocytosis  of  living 
parasites  even  in  the  spleen.  In  bird  malaria,  however,  Danilewsky^ 
(14)  and  Cardamatis  (4)  have  described  phagocytic  destruction  of 
parasites  by  leucocytes,  and  also  by  the  large  endothelial  cells 
(macrophages)  of  the  spleen.  Labbe  (22,  p.  239)  on  the  other  hand, 
states  that  these  parasites  live  voluntarily  in  such  cells. 

The  leucocytes  described  as  being  phagocytic  in  malaria  are 
almost  entirely  the  large  mononuclear  or  hyaline  corpuscles,  and 
the  relative  increase  of  these  during  the  disease  notwithstanding  a 
marked  decrease  of  the  total  number  of  leucocytes  in  the  general 
circulation  (leucocytopenia)  is  another  argument  in  favour  of 
phagocytosis  being  at  any  rate  a  factor  in  recovery,  if  not  the  sole 
cause  of  immunity  in  this  disease. 

Malaria  is  further  interesting  as  being  one  of  the  few  human 
protozoal  diseases  in  which  a  certain  tolerance  may  be  established 
between  host  and  parasite.  This  tolerance  may  be  fairly  permanent, 
as  in  many  natives  in  malarial  districts,  or  quite  temporary,  as  in 
patients  subject  to  frequent  relapses.  In  these  cases  a  few  parasites 
remain  over  in  the  host,  and  it  must  be  assumed  that  these  have  in 
some  way  become  resistant  to  the  phagocytes,  antibodies,  quinine, 
or  whatever  generally  causes  their  destruction,  and  that  it  is  only 

*  Most  of  Danilewsky's  much-quoted  experiments  had  to  do  with  the  injection  of  ma- 
larial blood  from  one  animal  into  another.  Under  these  conditions,  the  foreign  coipuscles 
themselves  are  immediately  devoured  by  phagocytes  and  therefore  the  contained  parasites 
are  also  gradually  digested  by  these  cells. 


I 


LEUCOCYTES  AND  PROTOZOA        961 

by  an  increase  of  this  resistance  or  by  a  lowering  of  the  host*s 
vitality  that  a  relapse  can  be  caused. 

No  observations  have  been  made,  so  far  as  we  can  ascertain,  as 
to  phagocytosis  of  other  parasites  normally  inhabiting  red  blood 
corpuscles,  as  for  example  the  Piroplasms  of  mammals,  and  the 
genera  Halteridium  and  Hsemoproteus  of  birds. 

The  only  known  instance  of  phagocytosis  of  trypanosomes  is 
after  their  inoculation  into  naturally  immune  or  immunised  ani- 
mals. The  blood  of  the  rat  about  ten  days  after  infection  with 
Trypanosoma  lewisi  may  swarm  with  parasites — their  number  being 
as  great  as  that  of  the  haematids.  Multiplication  then  ceases  and  the 
parasites  die  out,  sometimes  rapidly;  but  there  is  no  evidence  to 
show  that  they  are  engulfed  by  phagocytes.  The  rat  is  then  immune 
against  a  fresh  infection  with  this  species  of  trypanosome,  and  this 
immunity  can  apparently  be  accounted  for  by  the  fact  that  the 
rat's  phagocytes  are  now  actively  hostile  to  the  parasites.  Laveran 
and  Mesnil  (26),  who  have  inoculated  T.  lewisi  into  the  peritoneal 
cavity  of  an  immunised  rat,  describe  the  seizing  of  the  active  try- 
panosomes by  the  ccelomic  leucocytes.  In  districts  infected  with 
trypanosomiases  the  big  game  and  some  other  indigenous  animals 
have  been  shown  to  act  as  reservoirs  of  trypanosomes.  The  explana- 
tion of  this  tolerance  is  still  obscure.  Cold-blooded  vertebrates  are 
hkewise  known  habitually  to  harbour  trypanosomes  or  trypano- 
plasms  in  their  blood,  and,  although  phagocytosis  seems  not  to  have 
been  recorded  in  such  cases,  it  would  appear  likely  that  it  takes 
place  at  some  stage  of  their  life  history. 

In  spite  of  the  leucocytes  appearing  to  have  so  little  direct  effect 
in  ordinary  cases,  yet  the  lethal  trypanosomiases,  at  any  rate,  are 
essentially  diseases  of  the  lymphatic  system.  In  sleeping  sickness 
there  is  an  enormous  proliferation  of  lymphocytes,  probably  due 
to  a  toxin  such  as  has  been  demonstrated  in  some  trypanosomes  (42). 
The  lymphatics  around  all  the  blood  vessels  become  crowded  with 
these  small  mononuclear  leucocytes  which  interfere  with  circula- 
tion to  the  brain,  giving  rise,  according  to  Bruce  (2),  to  the  charac- 
teristic symptoms  of  the  disease. 

Before  discussing  further  the  nature  of  tolerance  and  other 
problems  relative  to  the  reaction  of  the  leucocytes  towards  protozoa, 
we  will  mention  briefly  other  parasites  known  to  infect  leucocytes. 


962        LEUCOCYTES  AND  PROTOZOA 

Classified  with  hsemamoebaB  among  the  Hsemosporidia  are  the 
closely  allied  Leucocytozoa.  The  Haemogregarines  which  used  to 
be  placed  with  them  are  now  known  to  have  closer  affinities  with 
Coccidia.  Certain  species  of  both  these  types  of  haemozoa  inhabit 
leucocytes,  while  closely  related  forms  live  in  red  blood  corpuscles. 
A  few  species,  e.g.,  Haemogregarina  agamss,  may  inhabit  either 
leucocytes  or  haematids,  and  therefore  the  nature  of  the  host  cell 
does  not  seem  to  be  of  great  systematic  importance. 

The  Leucocytozoa,  restricted  so  far  as  is  known  to  birds,'  are 
found  in  blood  corpuscles  which  are  sometimes  fusiform  in  shape, 
and  are  so  altered  in  appearance  that  it  is  difficult  to  make  out 
whether  they  were  originally  leucocytes  or  haematids.  However,  as 
a  rule,  they  appear  to  be  leucocytes,  as  in  the  case  of  L.  lovati 
(Fantham,  15)  of  the  grouse.  Leger  (27)  has  shown  that  while  the 
infected  corpuscles  are  mononuclear  leucocytes  in  the  case  of  crows, 
which  he  has  found  so  frequently  parasitised  in  the  Champagne 
district,  in  the  case  of  Leucocytozoa  ziemanni  from  the  great  owl 
the  infected  corpuscles  are  erythroblasts.  These  haematids  are  also 
shown  by  Franca  (16)  to  be  the  corpuscles  parasitised  in  the  case  of 
the  blackbird  and  hawk. 

Thus  we  must  conclude  that  either  kind  of  blood  corpuscle  can 
serve  as  host  to  various  species  of  Leucocytozoa.  Several  young 
parasites  are  sometimes  found  in  one  host  cell,  and  it  is  fairly  com- 
mon to  find  two  adults  of  the  same  or  opposite  sex  inhabiting  the 
same  cell,  fragments  of  which  remain  round  the  parasites  even  during 
reproduction.  They  appear  to  do  no  harm  except  to  the  individual 
cell  infected;  the  slender  evidence  pubHshed  by  Wickware  (49)  as 
suggestive  of  L.  anatis  being  the  cause  of  a  fatal  outbreak  of  disease 
among  ducks  near  Ottawa  has  not  been  confirmed. 

Haemogregarines  are  found  in  the  blood  of  all  classes  of  verte- 
brates, but  chiefly  in  those  with  cold  blood,  such  as  fishes  and  repn 
tiles.  In  these  latter  they  generally  inhabit  the  red  corpuscles,  but 
in  mammals  they  occur  more  usually  in  leucocytes.  They  can  be 

'  The  invertebrate  host  is  not  known,  but  is  almost  sure  to  be  one  of  the  etoparasites 
(fleas,  lice,  etc.)  infesting  the  birds.  There  evidently  is  a  cold-blooded  host,  for  it  is  only 
when  the  blood  is  put  on  a  cold  slide  that  ripe  microgametes  become  free  and  active,  that 
is,  "exflagellate,"  as  in  the  malarial  parasites.  The  transmitting  agent  can  be  determined 
only  by  examining  early  stages  of  infection  in  nestlings.  Leucocytozoa  are  reported  to  be 
common  in  some  parts  of  England,  e.g.,  Bournemouth  (9),  but  we  have  not  found  them  in 
many  different  kinds  of  birds  examined  in  the  Oxford  neighbourhood. 


fl 


LEUCOCYTES  AND  PROTOZOA  963 

distinguished  from  true  Leucocytozoa  since  they  have  a  different 
life  histor3%  for  instance  they  do  not  "exflagellate."  Sometimes  the 
body  of  the  parasite  is  enclosed  in  a  distinct  membrane  which  no 
doubt  helps  to  protect  it  from  the  digestive  action  of  its  host.  As  a 
rule  they  have  very  little,  if  any,  pathogenic  effect  except  on  the 
one  cell  parasitised.  Among  Haemogregarines  is  included  the  first 
intracorpuscular  parasite  discovered,  namely  Drepanidium  of  the 
frog  (Lankester,  1871).  This  harmless  form  has  been  seen  to  be 
devoured  by  phagocytes  (22),  and  so  has  the  more  destructive 
Karyolysus  of  lizards.  Haemogregarina  muris,  which  occurs  as  a 
harmless  parasite  in  the  leucocytes  of  wild  rats,  has  been  described 
by  Miller  (33)  as  causing  lethal  epidemics  among  tame  white  rats. 
This  is,  however,  an  intracellular  parasite  of  the  liver,  but  after 
schizogony  the  merozoites  pass  into  the  capillaries  and  are  taken  up 
by  the  leucocytes,  where  they  increase  in  size  and  make  themselves 
generally  at  home  until  such  time  as  they  may  be  taken  up  by  the 
invertebrate  host  (rat  mite). 

The  other  Protozoa  inhabiting  leucocytes  are  the  various  species 
of  Leishmania  and  Toxoplasma.  Since  the  latter  genus  has  been 
shown  by  Splendore  (48)  to  develop  a  flagellated  stage  in  cultures, 
as  was  proved  first  by  Rogers  for  Leishmania,  both  these  genera 
may  be  included  among  Flagellates  and  be  considered  together. 
The  parasites  as  found  in  the  vertebrate  host  are  small  oval  or 
rounded  bodies  multiplying  by  fission  and  generally  inhabiting 
mononuclear  leucocj'tes.  Fig.  2,  or  large  endothelial  cells.  Fig.  3; 
but  occasionally  they  are  found  in  polymorphonuclear  leucocytes. 

According  to  Laveran  (25)  the  genus  Leishmania  contains  two 
species  only:  L.  donovanit  the  cause  of  visceral  leishmaniasis,  and 
L.  tropicat  giving  rise  to  cutaneous  leishmaniasis,  including  the 
well-known  Tropical  Sore  {Bouton  d'orient)  of  the  Mediterranean 
regions,  and  the  various  forms  of  American  leishmaniasis. 

Visceral  leishmaniasis  in  India  takes  the  form  of  the  deadly 
disease  commonly  known  as  Kala  Azar;  the  milder  Mediterranean 
form  generally  occurs  in  children  or  dogs. 

Toxoplasma  has  now  been  recorded  from  several  animals  (37), 
but  the  original  and  best-known  species  is  T.  gondii^  recorded  by 
Nicolle  and  Manceaux  from  the  gondi  of  Tunisia. 

The  symptoms  of  both  visceral  leishmaniasis  and  toxoplasmiasis 


964        LEUCOCYTES  AND  PROTOZOA 


EXPLANATION  OF  ILLUSTRATION 

The  Figures  were  drawn  with  a  camera  lucida  at  a  magnification  of  1600,  except 
Fig.  7,  which  is  magnified  only  600  times. 

Fig.  I.  Entamoeba  gingivalis,  containing  leucocytes  undergoing  digestion,  n,  nucleus 
of  Entamoeba;  nl,  nucleus  of  half  digested  leucocyte;  np,  nucleus  of  polymorphonuclear 
leucocyte. 

Ehrlich's  Hsem.  and  Orange  G. 

Fig.  2.  Mononuclear  leucocyte  of  a  mouse  containing  several  Toxoplasma  t.  The 
nucleus  of  the  leucocyte,  which  is  degenerating. 
Iron  Hsematoxylin  and  Licht  Grun. 

Fig.  3.  Endothelial  cell  of  a  mouse  containing  numerous  Toxoplasma  t.,  actively 
dividing.  Note  the  hypertrophied  and  necrotic  nucleus  of  the  host  cell,  nb. 
Iron  Haematoxylin  and  Licht  Grun. 

Fig.  4.  Section  of  a  "  Plasmodium "  of  Myxocystis  from  the  sperm  sac  of  Tubijex 
rivulorum,  showing  covering  of  fine  processes,  vegetative  nuclei,  n,  and  spores,  sp. 
Iron  Haematoxylin  and  Pieronigrosin. 

Fig.  5.  Blood  of  Carcinus  msenas,  equal  portions  of  two  preparations:  a.  Normal 
Blood  showing  4  leucocytes,  /. 

Iron  Haematoxylin  and  Orange  G. 

b.  Infected  with  Thelohania,  showing  young  trophozoites,  p,  with  spherical  nuclei 
and  no  leucocytes. 

Giemsa. 

Fig.  6.  Leucocyte  of  Arenicola  ecandata,  living. 

Fig.  7.  Section  through  a  cyst  containing  a  pair  of  associated  trophozoites  of 
Conospora  arenicohe,  p,  undergoing  degeneration,  and  showing  the  accumulation  of 
leucocytes,  /,  outside  the  cyst,  c. 

Iron  Haematoxylin  and  Picrorosine. 

Fig.  8.  A  small  portion  of  a  cyst  similar  to  that  shown  in  Fig.  7,  more  highly  mag- 
nified, p,  Gonospora  degenerating;  /,  leucocyte. 

Fig.  9.  Leucocyte  of  Lumbricus,  living,  pr,  membranous  process. 

Fig.  10.  Leucocyte  of  Lumbricus,  fixed  in  Iodine  to  show  the  expanded  membra- 
nous processes,  pr. 


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LEUCOCYTES  AND  PROTOZOA  965 

include  hypertrophy  of  the  spleen,  in  which  organ  parasites  may  be 
found  often  when  absent  from  the  peripheral  blood.  This  spleno- 
megaly is  accompanied  by  more  or  less  fever  and  a  marked  leucocyto- 
penia.  The  colourless  corpuscles,  one  of  which  is  normally  present 
to  about  625  red,  may  disappear  until  there  is  only  i  to  2000  or 
more  haematids.  Notwithstanding  this,  there  is  in  leishmaniases, 
as  also  in  malaria  and  trypanosomiases,  a  marked  increase  of  large 
mononuclear  corpuscles  relative  to  polymorphonuclear.  In  fact  this 
condition  appears  to  be  characteristic  of  protozoal  diseases  as  dis- 
tinct from  bacterial,  in  which  the  polymorphonuclear  leucocytes 
are  in  somewhat  greater  excess  than  normally.  In  protozoal  diseases 
also  the  leucocytopenia  appears  to  be  lasting,  not  merel}'^  transient 
as  in  pyogenic  (45)  and  some  other  bacterial  infections  (44),  where 
the  leucocytes  only  appear  to  collect  temporarily  in  the  blood  vessels 
of  the  viscera,  especially  the  lungs,  liver,  and  spleen,  and  soon 
reappear  in  the  peripheral  circulation.  In  fact  the  behaviour  of 
many  protozoa  suggests  that  they  are  able  to  secrete  a  leucocyto- 
toxin,  and  this  has  already  been  shown  to  be  the  case  in  the  blood  of 
leishmaniasis  patients  (29). 

We  pass  now  to  the  consideration  of  Invertebrates,  whose 
leucocytes  correspond  roughly  to  those  of  Vertebrates  in  behaviour, 
variety  of  form  and  in  the  staining  property  of  their  granules — 
see  KoIIman  (21).  The  first  fact  to  strike  one  is  that  in  the  Inverte- 
brata  no  Protozoa  have  been  shown  to  inhabit  an  unchanged 
leucocyte.  Mrazek  (34)  certainly  claims  that  the  relatively  huge 
masses  floating  in  the  ccelomic  fluid  of  some  aquatic  Oligochaetes, 
e.g.,  Tubifex  and  Limnodrilus,  and  originally  said  to  be  the  plasmo- 
dia  of  Myxocystis  with  thousands  of  sp)ores,  are  in  reality  greatly 
hypertrophied  leucocytes  containing  thousands  of  Microsporidia. 
This  point  requires  further  investigation,  and  if  true  in  the  case 
of  Myxocystis  will  probably  also  prove  to  be  true  with  Dubosquia 
legeri  (36a),  parasitic  in  the  white  ant.  A  section  of  this  floating 
mass,  with  its  covering  of  fine  cilia-Iike  processes  and  the  developing 
spores  of  Myxocystis  contained  in  it,  is  figured  from  the  sperm-sac 
of  Tubifex  (Fig.  4). 

These  rather  rare  parasites  belong  to  the  little  understood 
Microsporidia,  and  there  is  always  difficulty  in  obtaining  hosts 
with  sufficiently  early  stages  to  determine  such  p>oints.  As  a  rule 


966        LEUCOCYTES  AND  PROTOZOA 

all  the  parasites  reach  a  certain  stage  at  almost  exactly  the  same 
time.  Another  and  better  known  genus  of  the  Microsporidia  is 
Nosema,  notorious  as  the  cause  of  epidemics  among  silkworms 
(pebrine  due  to  N.  bombycis)  and  among  honey-bees  (A/,  apis). 
But  it  does  not  seem  definitely  established  that  phagocytosis  occurs 
in  these  insects,  which  have  few  and  relatively  inactive  leucocytes. 
Metchnikoff  (31),  however,  states  that  the  spores  of  Microsporidia 
are  to  a  slight  extent  attacked  in  Daphnia. 

In  many  cases,  far  from  being  able  to  deal  with  such  parasites 
as  Microsporidia,  the  leucocytes  seem  to  disappear  from  the  blood 
when  infected.  Perez  (1904)  has  recorded  this  fact  in  a  crab 
{Carcinus  maenas)  infected  with  Tbelobania  msenadis;  and  in  a 
specimen  from  Plymouth,  which  was  found  and  passed  on  to  us 
by  the  late  Capt.  Geoffrey  Smith,  the  blood  was  swarming  with 
minute  trophozoites  of  this  parasite  (Figs.  $a  and  b).  Apparently  in 
consequence  of  this  hardly  a  leucocyte  could  be  found  in  the  blood, 
which  had  also  lost  its  power  of  coagulation,  so  that  the  crab 
gradually  bled  to  death  on  having  a  portion  of  one  of  its  append- 
ages removed.  Of  course  it  is  possible  that  the  leucocytes  had 
taken  refuge  in  one  of  the  lymphoid  glands;  it  would  be  interesting 
to  examine  these,  and  also  to  test  the  blood  for  a  leucocytotoxin. 
Unfortunately  we  have  not  succeeded  in  obtaining  further  infected 
specimens;  they  appear  to  be  rare  at  Plymouth  and  in  the 
Solent,  where  we  have  examined  over  a  hundred  crabs  without  find- 
ing any. 

Passing  to  the  true  Sporozoa,  we  find  various  families  of 
Gregarines  living  in  the  body-cavities  of  Annelids,  Insects,  and 
Echinoderms.  In  each  group  the  parasite  is  sooner  or  later 
drastically  dealt  with  by  the  leucocytes  of  the  host.  The  struggle 
between  Monocystis  and  the  phagocytes  of  the  Earthworm  is  one 
of  the  historic  cases  dealt  with  by  Metchnikoff  (31).  Another 
instance  is  found  in  the  marine  polychsete,  Arenicola  ecaudata,  the 
coelom  of  which  is  generally  infested  with  a  large  Gregarine, 
Gonospora  arenicolaSy  often  seen  in  large  numbers  and  in  various 
stages  of  development.  It  is  from  the  spores  hatched  in  the  ali- 
mentary canal  that  the  young  gregarine  or  sporozoite  penetrates 
the  wall  of  the  intestine  and  eventually  passes  into  the  coelom. 
Here  it  generally  becomes  secondarily  attached  by  means  of  an 


LEUCOCYTES  AND  PROTOZOA  ^ 

elongated  epimerite  to  the  body-wall  or  nephridial  ccelomostome. 
Thousands  of  such  parasites  (trophozoites)  may  be  found  in  the 
ccelom  growing  to  quite  a  large  size,  and  apparently  ignored  by 
the  host.  Having  completed  their  growth  such  trophozoites  normally 
associate  in  pairs,  and  secrete  round  themselves  a  cyst  which  may 
be  as  much  as  2  mm.  in  diameter.  At  this  stage,  indeed,  as  soon 
as  the  protoplasm  ceases  its  violent  streaming  movements,  the 
parasites  are  vigorously  attacked  by  the  host's  leucocytes,  which 
are  extraordinarily  active.  Unable  to  deal  singly  with  such  a  large 
body  as  the  cyst,  they  co-operate,  spreading  over  its  surface 
until  the  cyst  is  enclosed  in  a  film  composed  of  flattened  leucocytes. 
Layer  upon  layer  of  these  cells  may  be  added  (Figs.  6  and  7),  and 
cysts  thus  smothered  in  a  thick  coat  can  be  found  in  all  stages  of 
degeneration.  Some  seem  to  succeed  in  completing  their  reproduc- 
tion and  form  normal  spores;  but  generally  the  associates  begin  to 
degenerate  at  an  early  state,  and  their  protoplasm  becoming  vacuo- 
lated they  finally  disintegrate.  Many  cysts  containing  spores  suff"er 
the  same  fate. 

Such  is  the  behaviour  of  the  leucocytes  towards  parasitic  Gre- 
garines  in  several  polychsete  worms,  as  described  in  the  works  of 
Siedlecki  (47)  and  Caullery  and  Mesnil  (5),  while  Cuenot  (12)  has 
given  a  similar  account  of  the  fate  of  a  gregarine  in  the  insect 
Gryllus.  In  the  echinoderms  Spatangus  and  Echinocardium  the 
gregarines  Urospora  and  Lithocystis  are  likewise  attacked  by 
leucocytes  in  large  numbers  (38).  This  strange  capacity  of  the  leu- 
cocytes of  the  Invertebrates  with  large  vascular  or  coelomic  spaces 
to  co-operate  for  defence  against  an  intruding  parasite  is  most 
remarkable.  It  has  long  been  known  that  in  these  animals  the 
leucocytes  have  a  tendency  to  join  to  form  so-called  "plasmodia" 
described  by  Geddes  in  the  Sea  Urchin  (17).  The  apparent  clotting 
of  the  blood  is  due  in  most  Invertebrates  merely  to  the  coalescence 
of  the  leucocytes  in  irregular  masses  and  strands.  Now  this  property 
of  "Plasmodium"  formation  appears  to  be  due  to  the  peculiar  char- 
acter of  the  "  pseudopodia "  of  the  leucocytes,  which  are  not  out- 
standing finger-shaped  or^spine-like  processes,  as  generally  depicted, 
but  delicate  membranous  folds  thrown  out  in  various  directions,  as 
described  by  one  of  us  in  the  worm  Glycera  in  1898  (18),  and 
further  dealt  with  in  a  forthcoming  paper. 


968        LEUCOCYTES  AND  PROTOZOA 

These  spreading  membranes  may  be  rapidly  extended  or  with- 
drawn, and  when  coming  into  contact  with  some  foreign  object 
quickly  spread  over  its  surface  as  a  thin  film  of  protoplasm.  They 
are  especially  well-developed  in  Annelids  (Figs.  6  and  9)  and 
Echinoderms;  and  that  they  are  not  artifacts,  but  are  present  on 
the  normal  corpuscles  floating  in  the  fluids  of  the  body,  may  be 
proved  by  dropping  the  fluid  into  a  dilute  watery  solution  of  iodine, 
when  the  membranes  will  be  found  fixed  in  an  expanded  condition 
(Fig.  10).  It  is  by  the  ready  junction  of  these  processes  that  the 
coalescence  of  the  leucocytes  takes  place  to  form  the  "plasmodia" 
which  so  quickly  surround  the  cysts  of  parasitic  protozoa;  but,  as 
Michel  maintained  (32),  the  cells  in  these  coalesced  masses  do  not 
really  lose  their  individuality,  and  may  on  occasion  regain  their 
independence. 

Although  there  are  few  records  of  Protozoa  being  submitted  to 
phagocytosis,  in  many  cases  they  have  not  been  studied  from  this 
point  of  view.  There  are  several  Ciliates  which  occur  in  the  body 
cavities  of  Invertebrates,  for  example.  Annelids  (46,  20),  Crustacea 
(7),  Sagitta  (19),  Strongylocentrotus  (38),  but  there  are  no  records 
of  their  being  destroyed  by  phagocytes,  except  in  the  case  of  the 
common  earthworm,  where  Keng  (20)  states  that  these  parasites  on 
becoming  quiescent  are  surrounded  by  leucocytes  and  may  some- 
times be  seen  contained  in  a  large  vacuole  of  a  phagocyte.  In  most 
cases,  observations  are  needed  as  to  the  life  histories  of  these  Cihates 
and  especially  as  to  their  ultimate  fate.  During  their  actively  moving 
stage  they  are  apparently,  as  one  would  expect,  quite  free  from 
molestation  by  leucocytes. 

From  the  review  of  the  subject  given  above  it  is  obvious  that 
much  research  is  still  necessary  before  reaching  definite  results. 
Nevertheless  we  may  attempt  to  indicate  provisional  conclusions 
that  may  be  drawn  with  regard  to  mutual  reactions  between  leu- 
cocytes and  protozoa  in  animals. 

As  regards  phagocytosis  Metchnikoff"  supposed  that  protozoa 
warded  off"  the  attack  of  leucocytes  by  their  active  movements. 
This  explanation  is,  however,  insufficient,  for  many  motionless 
forms  are  just  as  free  from  attack  as  are  the  tissues  themselves  or 
the  genital  products  floating  in  the  ccelom.  However,  just  as  the 
ova  and  spermatozoa  in  such  cases  may  be  attacked  under  certain 


LEUCOCYTES  AND  PROTOZOA  969 

conditions  (43,  6)  so  it  is  with  the  parasites.  It  must  also  be  remem- 
bered that  all  the  sporozoa  pass  a  certain  stage  of  their  life  history 
actually  in  the  cells  of  the  host,  and  that  many  of  them,  like  the 
Coccidia,  continue  to  live  in  the  tissues  quite  unharmed  by  leuco- 
cytes. Some  would  attribute  this  immunity  from  attack  to  the  leu- 
cocytes being  merely  indifferent  to  the  protozoa.  This  explanation, 
however,  is  not  satisfactory,  since  it  is  well  known  that  the  most 
inactive  substances,  such  as  carbon  or  glass,  are  rapidly  ingested 
by  phagocytes.  We  must  then  conclude  that  these  protozoal  para- 
sites are  avoided  by  the  leucocytes  owing  to  the  secretion  of  some 
substance  which  renders  them  negatively  chemiotactic. 

Further  we  may  conclude  that  the  defences  against  invading 
organisms  are  far  better  developed  in  Vertebrates  than  in  Inverte- 
brates. No  case  seems  yet  to  have  been  discovered  in  a  Vertebrate 
of  a  bacterium  living  habitually  in  the  fluids  of  the  body,  in  other 
words,  no  bacterium  has  succeeded  in  establishing  a  condition  of 
tolerance  either  in  the  ccelom  or  in  the  blood  vascular  system.  This 
failure  of  the  bacteria  is  due  either  to  the  phagocytic  action  of  the 
leucocytes,  or  to  the  secretion  of  efficient  bactericidal  substances. 
On  the  other  hand,  in  the  Invertebrates  cases  are  known  of  the 
habitual  presence  of  bacteria  in  the  coelomic  fluid;  as  for  instance 
in  the  common  earthworm  (20);  and  certain  protozoa  have  suc- 
ceeded in  thus  establishing  themselves  in  Vertebrates  as  well  as 
Invertebrates. 

Such  constant  parasites  are  said  to  be  tolerated  by  the  host. 
Since  the  parasites  are  characteristically  capable  of  reproducing  in 
enormous  numbers,  tolerance  can  only  be  explained  as  due  to  a 
balance  having  been  established  between  their  reproductive  powers 
and  the  destructive  powers  of  the  host.  It  is  obvious  that  such  a 
state  cannot  be  permanent — sooner  or  later  the  balance  must  be 
upset,  perhaps  owing  to  some  change  in  external  conditions,  and 
either  host  or  parasite  will  gain  the  upper  hand.  Tolerance  then  is 
only  a  stage  between  disease  and  immunity.  The  total  absence,  for 
instance,  of  coelomic  Gregarines  from  Arenicola  grubei  and  their 
constant  presence  in  A.  ecaudata^  when  both  these  species  live 
together  in  the  sand  under  identical  conditions,  is  probably  to  be 
explained  as  due  to  A.  grubei  having  passed  through  the  stage  of 
tolerance  to  that  of  immunity.  The  same  explanation  probably 


970       LEUCOCYTES  AND  PROTOZOA 

applies  to  similar  phenomena  among  other  groups  of  animals  which 
at  first  sight  appear  so  mysterious. 

It  is  by  no  means  yet  certain  whether  "protozoocidal"  substances 
are  really  secreted  by  the  host,  though  it  seems  to  be  clear,  on  the 
other  hand,  that  in  some  cases  protozoa  secrete  toxins.  The  protozoa, 
perhaps  owing  to  their  relatively  high  organisation,  are  more  capable 
of  resisting  the  attacks  of  their  host  than  bacteria.  At  the  same  time, 
owing  to  their  complicated  life  histories,  it  is  often  necessary  for  pro- 
tozoa to  reach  another  host  before  further  multiplication  can  take 
place,  and  therefore  they  are  effectually  prevented  from  overcrowd- 
ing and  killing  their  host.  The  combination  of  these  factors  in  the 
case  of  protozoa  must  help  considerably  towards  the  establishment 
of  tolerance. 

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32.  Michel,  "Sur  la  pretendue  fusion  des  cellules  lymphatiques  en  plas- 

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FURTHER  OBSERVATIONS  ON  THE  EFFECTS  OF 
ROENTGENIZATION  AND  SPLENECTOMY  ON 
ANTIBODY   PRODUCTION 

By  Ludvig  Hektoen,  M.D.,  Chicago,  III. 

(From   the  John   McCormick   Institute   for   Infectious   Diseases,   Chicago) 

IN  previous  papers  (i)  I  have  recorded  observations  which  show 
that  exposure  of  white  rats,  dogs,  and  rabbits  to  the  roentgen 
ray  at  about  the  same  time  that  antigen  is  introduced  may 
restrain  greatly  the  production  of  antibodies  as  measured  by  the 
antibody  content  of  the  serum.  I  have  also  noted  (2)  that  in  dogs 
splenectomy  just  before  the  injection  of  foreign  blood  was  followed 
by  a  lower  but  otherwise  typical  antibody  curve  than  is  usually  the 
case  in  dogs  under  otherwise  comparable  conditions.  In  the  mean- 
time additional  observations  have  been  made  on  roentgenization 
and  splenectomy  under  more  diversified  conditions,  the  results  of 
which  seem  to  merit  a  brief  report. 

Splenectomy.  Experiments  on  white  rats  gave  results  similar  to 
those  in  dogs.  Without  exception  the  amount  of  lysin  for  sheep 
corpuscles  was  much  less  in  the  rats  in  which  the  spleen  was  removed 
at  the  same  time  that  the  blood  was  injected.  As  seen  on  Chart  I  the 
lysin  curves  present  the  same  general  outHnes,  but  in  the  splenecto- 
mized  series  the  latent  period  is  longer,  the  height  and  duration  less 
than  in  the  controls. 

Rats  weighing  from  70  to  80  grams  were  used;  i  c.c.  of  a  10  per  cent 
suspension  of  sheep  blood  per  kilo  of  weight  was  injected  intramuscularly 
immediately  after  the  splenectomy.  The  curves  (Chart  I)  are  composite 
curves  based  on  the  titers  of  two  rats  killed  on  each  day  indicated,  it 
being  practically  impossible  to  bleed  the  same  rat  many  times.  The 
control  curve  gives  the  titer  of  rats  of  the  same  age  and  size,  treated  in 
the  same  way,  but  not  splenectomized.  The  titer  gives  the  highest 
dilution  of  the  serum  that  caused  distinct  lysis  in  a  mixture  of  0.6  c.c. 
consisting  of  0.2  c.c.  of  a  5  per  cent  suspension  of  sheep  corpuscles,  well 
washed,  0.0125  c.c.  of  guinea  pig  serum,  and  the  indicated  amount  of 

973 


974    ROENTGENIZATION  AND  ANTIBODY  PRODUCTION 

heated  rat  serum,  the  rest  being  salt  solution.  The  tubes  were  incubated 
for  two  hours  and  then  placed  in  the  ice-box  until  the  next  morning. 

Chart  I.  Lvsin  in  Normal  and  Splenectomized  Rats 


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In  rabbits  splenectomy  from  one  to  six  days  before  the  intra- 
p>eritoneaI  injection  of  25  c.c.  of  sheep  blood  as  a  rule  did  not  inter- 
fere with  the  production  of  lysin  and  precipitin;  exceptionally, 
however,  splenectomy  shortly  before  the  injection  seemed  to  suspend 
completely  the  advent  of  antibodies  into  the  blood  (Table  I). 

Table  I. — ^Antibody  Production  in  Rabbits  Injected  with  Sheep  Blood  before 

Splenectomy 


Days 
after 
Injec- 
tion OF 
Antigen 

Splenectomy 

Three  Days 

BEFORE  Injection 

OF  Antigen 

Splenectomy 

Three  Days 

BEFORE  Injection 

OF  Antigen 

Splenectomy 

Six  Days 

before  Injection 

OF  Antigen 

Splenectomy 

Nine  Weeks 

BEFORE  Injection 

OF  Antigen 

Lysin  |  Precipitin 

Lysin  |  Precipitin 

Lysin  |  Precipitin 

Lysin  |  Precipitin 

4 

0    1        0        1 

3072  1         100     1 

192  1             0 

3072  1             0 

6 

384     1         0 

3072  1       2400 

768  1       1600 

12288  1         200 

9 

48     1         0 

12288  1       4800 

1536  1       6400 

24576  1       3200 

11 

0     1         0 

12288  1       6400 

3072  1       6400 

24576  1       6400 

14 

96     1         0 

12288  1     12800 

6144  1     12800 

24576  1     12800 

16 

0     1         0 

6144  1     25600 

6144  1     12800 

12288  1     12800 

19 

24     1         0 

6144  1     25600 

6144  1     12800 

6144  1       6400 

21 

0     1         0 

3072  1     25600 

6144  1     12800 

6144  1       3200 

24 

0     1         0 

3072  1     19200     1     6144  |     12800 

1 

ROENTGENIZATION  AND  ANTIBODY  PRODUCTION    975 

Of  six  rabbits  splenectomized  five  to  nine  weeks  before  the  in- 
jection all  save  one  developed  about  the  usual  amount  of  lysin  and 
also  precipitin  in  fairly  high  degree,  though  with  a  somewhat  pro- 
longed latency  (Table  I).  Of  ten  rabbits,  all  young  and  healthy, 
splenectomized  from  five  to  nine  weeks  before  the  intraperitoneal 
injection  of  30  c.c.  of  human  blood,  all  but  one  failed  to  develop 
more  than  a  trace  of  precipitin,  but  in  all  agglutinin  of  considerable 
strength  developed  as  well  as  smaller  amounts  of  lysin  (Table  II). 
This  last  result  is  of  interest  because  it  indicates  that  under  certain 
conditions  splenectomy  even  some  time  before  immunization  may 
restrain  the  formation  of  one  kind  of  antibody  more  than  others. 

Table  II. — Antibody  Production  in  Rabbits  Injected  with  Human  Blood  Nine 

AND  Six  Weeks  after  Splenectomy 


Days  after 

Injection 

of  Antigen 

Splenectomy  Nine  Weeks 
BEFORE  Injection  of  Antigen 

Splenectomy  Six  Weeks 
BEFORE  Injection  of  Antigen 

Lysin      |  Agglutinin  |  Precipitin 

Lysin  |     Agglutinin  |  Precipitin 

4 

0       1           96       1             0 

0  1               96       1             0 

6 

0       1         192       1             0 

0  1             384       1             0 

9 

96       1       3072       1             0 

0  1           3072       1             0 

11 

192       1       6144       1             0 

384  1           6144       1       1600 

14 

384       1       3072       1              0 

384  1           3072       1       1600 

16 

192       1       3072       1         200 

384  1            1536       1             0 

19 

192       1       1536       1             0 

192  1              768       1             0 

21 

96       1         192       1             0 

192  1             768       1             0 

26 

96       1         192       1             0 

96  1             192       1             0 

In  the  experiments  25  c.c.  of  sheep  or  human  blood  were  injected 
intraperitoneally  in  one  dose.  The  figures  in  the  tables  give  the  highest 
active  dilution  of  the  serum  in  the  case  of  the  lysin  and  agglutinin  tests, 
and  the  highest  dilution  of  sheep  or  human  blood  in  which  the  rabbit  serum 
caused  precipitate  by  the  ring  or  contact  method  after  two  hours  at  the 
room  temp>erature  in  case  of  the  precipitin  tests.  The  lysin  and  agglutinin 
tests  were  carried  out  in  mixtures  of  0.6  c.c.  containing  0.2  c.c.  of  a  5  per 
cent  suspension  of  washed  corpuscles,  heated  rabbit  serum,  and  in  the 
lysin  tests  guinea  pig  serum  (complement),  the  rest  being  salt  solution. 
The  complement  dose  was  .006  c.c.  in  the  tests  for  lysin  for  sheep  cor- 
puscles, and  .02  c.c.  in  the  tests  for  lysin  for  human  corpuscles.  All  lysin 
and  agglutinin  mixtures  were  incubated  for  two  hours  and  then  placed 
in  the  ice  box  until  the  next  morning. 


976    ROENTGENIZATION  AND  ANTIBODY  PRODUCTION 

Taken  as  a  whole  my  results  correspond  well  enough  with  those  of 
earlier  observers,  some  of  whom  obtained  inhibition  of  antibody 
production  from  splenectomy  (London  (3),  Deutsch  (4),  while  others 
failed  (Jakuschewitsch  (5),  Kraus  and  SchifFmann  (6),  McGowan  (7)), 
but  minute  comparisons  are  not  worth  while  because  of  great  differ- 
ences in  the  experiments,  e.g.,  mode  of  injection  of  antigen,  measure- 
ments of  antibodies,  etc. 

Splenectomy  and  Roentgenization.  Table  III  gives  details  of  an 
experiment  on  young  dogs  of  the  same  litter  in  which  roentgeniza- 
tion and  splenectomy,  alone  and  combined,  greatly  reduced  the 
output  of  lysin  after  injection  of  goat  blood.  The  small  number  of 
dogs  represented  precludes  any  conclusion  as  to  which  procedure 
may  be  most  effective,  but  the  results  of  splenectomy  alone  or 
combined  with  roentgen  ray  shortly  before  the  antigen  was  injected 
seem  the  more  striking. 

Table  III. — Roentgen  Ray  (45  Kienbach  Units)  and  Splenectomy,  Singly  and 
Combined,  Shortly  before  and  Five  Days  after  Injection  of  Goat  Blood 
IN  Dogs 


1 

2 

Roentgen 

Ray 

3  and  4 
Roentgen 

5 

6 
Splenec- 
tomy 

7 

Days 

Roentgen 

Two  Days 

Ray 

Splenec- 

One Day 

after 

Ray 

before 

Two  Days 

tomy 

before 

Injection 

Two 

Injection 

and 

One 

AND 

Control 

OF 

Days 

AND 

Splenectomy 

Day 

Roentgen 

Goat 

before 

Splenec- 

One Day 

before 

Ray 

Blood 

Antigen 

tomy 

Five  Days 

after 

before 
Injection 

Injection 

Five  Days 

AFTER 

Injection 

2 

0 

0 

0     1     0 

0 

0 

48 

3 

0 

0 

0     1     0 

48 

48 

192 

4 

0 

0 

0     1     0 

96 

48 

348 

S 

96 

96 

48     1     0 

0 

192 

768 

6 

384 

96 

48     1     0 

0 

384 

1536 

7 

384 

192 

48     1  48 

96 

384 

3072 

8 

768 

384 

96     1  48     1 

0 

384 

3072 

9 

768 

384 

96     1  48 

0 

384 

3072 

10 

11 

192 

96 

48     1  48     1 

192 

192 

1536 

12 

192 

96 

48     1  48 

0 

192 

768 

13 

192 

96 

48     1  48 

0 

192 

384 

14 

15 

96 

0 

0     1     0 

0 

48 

192 

16 

17 

96 

0 

0     1     0 

0 

96 

192 

18 

96 

0 

0    1    0    1 

0 

48 

192 

ROENTGENIZATION  AND  ANTIBODY  PRODUCTION    977 

In  this  as  well  as  the  other  experiments  now  discussed  the  roentgeniza- 
tion  was  done  in  the  Presbyterian  Hospital  by  Earl  Ball.  The  Coolidge 
tube  was  used,  the  focal  distance  was  8  inches,  the  current  5  to  6 
milliamperes,  spark-gap  8  inches.  In  the  tables  the  dose  is  expressed  in 
calculated  Kienbach  units.  Usually  two  exposures  were  given,  a  major 
and  one-fourth  as  long  the  next  day. 

Table  IV. — Roentgen  Ray  (45  Kienbach  Units)  and  Splenectomy,  Singly  or  Com- 
bined, IN  Docs  AT  OR  Near  Height  of  Production  of  Lysin  for  Goat 
Corpuscles 


Days  after 
Injection  of 
Goat  Blood 

1 
Roentgen 

Ray  on 
Sixth  Day 

2 

Splenectomy 

on 

Sixth  Day 

3  AND  4 

Splenectomy  on  Sixth  Day 

AND  Roentgen  Ray 

on  Seventh  Day 

5 
Control 

3 

4 

192 

192 

96 

5 

768 

768 

192        768 

384 

6 

768 

768 

384       1536 

768 

7 

1536 

1536 

768       3072 

768 

8 

3072 

1536 

1152       1536 

1536 

9 

3072 

3072 

1152       1536 

1536 

10 

6144 

3072 

1536       1536    1    1536 

11 

3072 

3072 

1536       1536 

1536 

12 

3072 

3072 

768       1536 

3072 

13 

1536 

768 

768        768 

768 

14 

1536 

768 

768        768 

768 

15 

1536 

384        768 

16 

1536 

768 

384        768 

768 

17 

384        768 

18 

1536 

768 

768 

19 

192        384 

20 

768 

384 

384 

21 

192        192 

22 

23 

192        192 

384 

24 

768 

384 

25 

26 

192        192 

192 

27 

28 

768    1     192 

192 

Roentgenization  and  Splenectomy  at  Height  of  Antibody  Produc- 
tion. Tables  IV  and  V  and  Chart  II  give  the  results  of  new  experi- 
ments (8)  on  the  effect  of  roentgen  ray  and  splenectomy  at  or  near 
the  high  point  of  the  accumulation  of  antibody  in  the  blood.  These 
results  indicate  that  neither  roentgenization,  as  practiced,  alone  or 
combined  with  splenectomy,  nor  splenectomy  alone  or  combined 


978    ROENTGENIZATION  AND  ANTIBODY  PRODUCTION 

with  roentgenization,  had  any  appreciable  influence  on  the  course 
and  amount  of  antibodies  in  the  blood  when  applied  several  days 
after  the  introduction  of  the  antigen.  The  experiments  covered  by 
Tables  IV  and  V  concern  in  each  case  young  dogs  of  one  but  not 
the  same  litter. 

Table  V. — Roentgen  Ray  (45  Kienbach  Units)  and  Splenectomy,  Singly  or  Com- 
bined, IN  Dogs  at  or  Near  Height  of  Production  of  Agglutinin  for  Rat 
Corpuscles 


Days  akier 

Injection  of 

Rat  Blood 

1 
Roentgen 

Ray  on 
Sixth  Day 

2 
Splenectomy 

ON 

Sixth  Day 

3  AND  4 

Splenectomy  ON  Sixth  Da  Y 

AND  Roentgen  Ray 

on  Seventh  Day 

5 
Control 

4 

96 

96 

1 

96 

5 

192 

192 

0    1      0 

192 

6 

192 

192 

192    1      96 

192 

7 

384 

384 

192    1     192 

384 

8 

768 

768 

384    1     384 

768 

9 

768 

768 

768    1     384 

768 

10 

768 

768 

768    1     576 

768 

11 

384 

768 

384 

12 

384 

384 

768    1     384 

384 

13 

384 

768 

384    1     384 

384 

14 

192 

384 

384    1     192 

384 

15 

384    1     192 

16 

384 

384 

192 

17 

384    1     192 

18 

384 

384 

192 

19 

384    1     192 

20 

192 

384 

192 

21 

384    1      96 

22 

23 

192    1      96 

24 

192 

384 

192 

25 

26 

96    1      96 

27 

28 

192 

384 

192 

Beginning  soon  after  splenectomy  the  red  corpuscles  were  found 
more  resistant  to  hypotonic  solution  than  corpuscles  of  non-splenec- 
tomized  animals.  The  increase  in  resistance  seemed  to  be  about  the 
same  in  the  splenectomized  animals  treated  with  roentgen  ray  as  in 
those  that  were  not;  there  was  no  change  from  the  normal  in  the 


ROENTGENIZATION  AND  ANTIBODY  PRODUCTION    979 

resistance  of  the  corpuscles  of  animals  subjected  to  the  ray  only.  In 
the  rabbits,  too,  splenectomy  as  a  rule  results  in  an  increase. 

Chart  II  illustrates  the  results  of  a  study  on  six  healthy  young 
rabbits,  each  injected  with  25  c.c.  sheep  blood,  and  in  two  of  which 
splenectomy  was  made  nine  and  ten  days  later,  but  without  any 
effect  whatever  on  the  precipitin  titer  as  compared  with  that  in 
the  controls. 

These  results  are  in  full  harmony  with  the  results  obtained  by 
London  (9)  in  an  experiment  on  the  effect  of  splenectomy  some 

Chart  II.  Splenectomy  at  Height  of  Anttibody  Curve 


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Oontrel   Rabbit* 
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days  after  the  production  of  hemolysin  had  started.  I  have  reported 
previously  that  roentgenization  of  dogs  when  antibody  production 
is  well  under  way  has  little  or  no  effect  on  the  antibodies  in  the 
blood  (10). 

Roentgenization  Sixteen  Days  before  the  Antigen  is  Introduced. 
Five  young  healthy  dogs  of  the  same  Htter  were  given  each  an  intra- 
venous injection  of  rat  blood;  sixteen  days  before  three  of  the  dogs 
had  been  exposed  to  roentgen  ray  for  fifteen  minutes  and  again  for 
three  minutes  the  day  after  (54  Kienbach  units).  Two  days  before 
the  injection  of  the  rat  blood  the  leucocytes  ranged  from  14,666  to 


98o    ROENTGENIZATION  AND  ANTIBODY  PRODUCTION 


17,000  in  the  roentgen  dogs  and  in  the  two  control  dogs  the  counts 
were  11,333  ^^^  15,666;  the  differential  counts  were  normal.  Table 
VI  shows  that  the  agglutinin  titer  ran  uniformly  higher  in  the  dogs 
treated  with  the  roentgen  ray  than  in  the  controls. 

Table  VI. — ^Agglutinin  Production   in  Dog  Previously  Exposed  to  Roentgen 

Ray  (45  Kienbach  Units) 


Days  akier 

Injection  of 

Rat  Blood 

Roentgen  Ray  Sixteen  Days  before 
Injection  of  Rat  Blood  and  again 
FOR  Three  Minutes  the  Next  Day 

Gdntrols 

1     1     2     1     3 

1     1     2 

3 

48    1      24    1      24 

96    1     48 

4 

384    1     192    1     384 

96    1     192 

5 

1536    1     192    1     384 

384    1     192 

6 

6144    1     768    1    1536 

768    1     192 

7 

6144    1     768    ]    3072 

1536    1     384 

8 

3072    1    1536    1    6144 

1536    1     384 

9 

6144    1    3072    1    3072 

1536    1     768 

10 

3072    1    3076    |    1536 

1536    1    1536 

11 

3072    1    3076    |    3072 

768    1    1536 

12 

1536    1    1536    1    3072 

768    1     384 

13 

1768    j    1536    1    1536 

768    1     384 

14 

354    1     768    1     384 

384    1     192 

16 

192    1     384    1     192 

192    1     192 

18 

192    1     384    1     192 

192    1     192 

22 

192    1     384    1      96 

192    1     48 

25 

96    1     192    1     45 

96    1     96 

In  another  experiment  three  dogs  were  exposed  to  roentgen  ray 
for  twenty  minutes  (60  Kienbach  units)  and  fifteen  days  later 
injected  with  goat  blood.  These  animals  developed  profound  effects 
and  died  a  few  days  after  the  injection  without  having  produced 
hardly  any  lysin. 

The  first  experiment  indicates  that  under  certain  conditions  the 
roentgen  ray  induces  such  changes  in  the  body  that  the  power  to 
elaborate  antibodies  is  increased.  It  fies  near  at  hand  to  associate 
this  increased  power  with  regenerative  changes  in  the  lymphatic 
tissues  and  spleen  after  roentgenization. 

In  all  the  experiments  on  dogs,  the  antigen,  i  c.c.  of  10  per  cent  suspen- 
sion of  goat  blood  or  rat  blood  per  kilo  of  weight  of  dog,  was  injected  in- 
travenously. Only  one  injection  was  given.  The  figures  in  the  tables  give 
the  highest  active  dilutions  of  the  dog  serums  in  mixtures  of  0.6  c.c. 
containing  0.2  c.c.  of  a  5  per  cent  suspension  of  washed  goat  or  rat  cor- 


I 


ROENTGENIZATION  AND  ANTIBODY  PRODUCTION    981 

puscles,  the  proper  amount  of  dog  serum,  0.0125  c.c.  guinea  pig  serum  in 
lysin  tests,  the  rest  being  salt  solution.  The  mixtures  were  incubated  for 
two  hours  and  kept  in  the  ice  box  until  the  next  morning. 

.  Summary.  The  results  recorded  show  that  splenectomy  may 
diminish  the  output  of  antibodies  especially  when  practiced  about 
the  same  time  the  antigen  is  injected.  In  the  rabbit,  however, 
splenectomy  under  certain  conditions  may  have  little  or  no  efiPect 
on  antibody  production,  as  after  a  single  large  dose  of  sheep  blood. 
On  the  other  hand,  even  when  made  several  weeks  before  injection 
of  human  blood,  removal  of  the  spleen  seemed  to  interfere  with  the 
formation  of  precipitin,  but  further  observations  are  needed  to 
determine  whether  such  selective  eflfect  occurs  regularly  under 
these  circumstances. 

On  the  whole,  the  eflfects  of  splenectomy  at  or  near  the  time  of 
injection  of  antigen  appear  variable  and  uncertain,  more  so,  perhaps, 
than  might  be  expected  from  the  demonstrations  that  antibodies 
appear  earlier  in  the  spleen  than  in  the  blood  (11),  that  antigen  is  fixed 
by  the  spleen  (12),  and  that  in  the  presence  of  antigenic  substances 
cultures  of  splenic  tissue  outside  the  bodymayproduce  antibodies  (13). 
And  yet  variations  in  results  are  really  not  surprising  if  we  consider, 
first,  the  close  relation  of  the  spleen  to  the  lymphatic  tissues  and 
the  marrow,  which  are  believed  also  to  take  part  in  the  elaboration 
of  antibodies  and  consequently  may  be  capable  of  compensatory 
activities,  to  say  nothing  of  the  possibilities  of  accessory  spleens; 
and,  secondly,  that  the  experiments  of  different  investigators  were 
made  under  diverse  conditions  in  such  important  respects  as  kind, 
quantity,  and  mode  of  injection  of  antigen,  measurement  of  anti- 
body, etc.  Perhaps  the  effects  of  splenectomy  would  not  be  so  vari- 
able in  larger  series  of  experiments  with  particular  effort  to  secure 
as  high  degree  of  constancy  as  possible  of  the  controllable  factors. 

The  results  of  several  experiments  indicate  clearly  that  after 
antibody  production  is  well  under  way,  splenectomy  has  little  or 
no  effect  on  the  course  of  the  antibodies  in  the  blood.  I  have  noted 
elsewhere  (14)  that  the  usual  effects  of  the  roentgen  ray  and  of  benzene 
appear  to  be  withstood  when  antibody  production  is  well  started. 
We  now  find  that  splenectomy  even  when  reinforced  with  roent- 
genization  seems  subject  to  a  similar  resistance;  at  any  rate  the 
antibody  content  of  the  blood  was  not  diminished  markedly  by 


982  ROENTGENIZATION  AND  ANTIBODY  PRODUCTION 

splenectomy  and  roentgenization  at  or  near  the  height  of  the  curve. 
The  nature  of  this  so-called  resistance  remains  obscure. 

It  may  be  pointed  out  again  that  as  time  passes  after  roent- 
genization the  power  to  produce  antibodies  may  be  increased,  and  it 
is  suggested  that  this  increase  may  be  due  to  regenerative  changes 
in  the  spleen  and  lymph  nodes.  We  consequently  must  distinguish 
between  the  immediate  and  the  later  efifects  of  the  roentgen  ray. 
That  the  ray  may  reduce  antibody  production  seemed  a  good  ex- 
planation of  the  increased  susceptibility  of  guinea  pigs  to  tubercu- 
losis described  by  Morton  (15);  Kellert  (16),  however,  could  not  confirm 
Morton's  claim;  he  found  that  roentgenization  rather  increased  the 
resistance  to  the  tubercle  bacillus  at  the  same  time  as  the  guinea 
pigs  seemed  to  become  more  susceptible  to  secondary  and  con- 
taminating infections.  Corper  (17)  also  failed  to  produce  any  distinct 
effect  on  the  gross  tuberculous  lesions  in  guinea  pigs  by  a  single 
exposure  to  the  roentgen  ray.  These  contradictory  results  invite 
further  experiments,  not  only  on  the  effect  of  roentgenization  on 
antibody  production,  but  also  on  phagocytosis  and  other  cellular 
activities. 

BIBLIOGRAPHY 

1.  J.  Inject.  Dxs.j  1915,  XVII,  415  and  1918,  XXII,  28. 

2.  Ibid,  1909,  VI,  78. 

3.  Arcb.  d.  Sc.  bioL,  190 1,  VIII,  328. 

4.  Ann.  de  I'lnst.  Pasteur,  1899,  XIII,  688. 

5.  Ztscbr.  J.  Hyg.  u.  Injectionskrankb.,  1904,  XLVII,  407. 

6.  Ann.  de  Vlnst.  Pasteur,  1906,  XX,  225. 

7.  J.  Patb.  &  Bacterial.,  191 1,  XV,  262. 

8.  See  Hektoen,  J.  Infect.  Dis.,  198,  XXII,  p.  28. 

9.  Arcb.,  d.  Sc.  bioL,  1901,  VIII,  p.  328. 
ID.  J.  Infect.  Dis.,  1918,  XXII,  p.  28. 

11.  PfeifFer  and  Marx,  Ztscbr.  f.  Hyg.  u.  Infektionskrankb.,  1898,  XXXVII, 

272.     Cantacuzene,  Ann.  de  I' Inst.  Pasteur,  1902,  XVI,  552.     Tsu- 
rumi  and  Koda,  Ztscbr.  f.  Immunitdtsfs.,  O.,  1913,  XIX,  519. 

12.  Leuckart  and  Becht,  Trans.  Cbicago  Patb.  Soc,  191 1,  VIII,  202. 

13.  Carrell  and  Ingebrigtsen,  J.  Exper.  M.,  1912,  XV,  287. 

14.  J.  Infect.  Dis.,  1918,  XXII,  28. 

15.  J.  Exper.  M.,  1916,  XXIV,  419. 

16.  J.  Med.  Researcb,  1918,  XXXIX,  93. 

17.  Am.  Rev.  of  Tuberculosis,  19 18,  II,  587. 


THE  IMPORTANCE  OF  RECORDING  THE  WEIGHT 

AT  DEATH 

By  Elliott  P.  Joslin,  M.D.,  Boston,  Mass. 

(Recently  Lt.  Col.  M.C.) 

INDIVIDUALS  die,  not  because  they  are  tall  or  short,  and  not 
always  because  they  are  fat  or  thin,  but,  save  in  the  case  of 
sudden  death,  life  usually  ends  with  a  loss  in  weight.  Yet  path- 
ologists record  with  precision  the  exact  height,  but  only  approx- 
imately note  the  weight.  The  simplicity  of  the  former  determina- 
tion and  the  inconvenience  of  the  latter  are  the  explanation  for  the 
neglect  to  record  more  accurately  the  more  important  of  these  two 
data. 

A  deeper  significance  than  the  mere  accumulation  of  facts  is 
attached  to  the  registration  of  the  weight.  Just  as  the  addition 
of  cellular  pathology  to  anatomical  pathology  and  the  later  addition 
of  bacteriology  broadened  the  scope  of  the  pathologist's  work,  the 
inclusion  of  the  weight  at  death  makes  a  new  demand  upon  the 
pathologist,  for  he  should  explain  deviations  from  the  normal,  and 
this  leads  him  into  the  fields  of  chemistry  and  physiology. 

The  army  hospital  centers  in  France  offered  a  favorable  oppor- 
tunity to  secure  body  weights  at  death.  Although  the  weights  of  the 
soldiers  during  the  few  weeks  previous  to  hospital  entrance  were  not 
known,  their  original  weights  at  entrance  into  the  army  will  become 
available,  as  well  as  the  army  tables  for  the  average  weight  for 
the  given  age  and  height.  These  considerations  led  me  to  enlist  the 
help  of  the  pathologist,  Lt.  Col.  David  Marine,  in  charge  of  all 
the  laboratories  at  the  Mesves  Center,  and  it  is  through  his  courtesy 
and  that  of  his  associates  that  the  following  facts  are  ref>orted.  It 
was  found  that  the  average  weight  at  death  of  each  man  in  a 
group  of  59  men  was  54  kilograms.  This  represented  a  loss  from  the 
normal  weight  of  men  of  their  average  height  and  approximate  age 
of  about  15  kilograms  (33  pounds) — 22  p>er  cent.  This  is  approxi- 
mately the  same  as  Benedict  found  the  loss  of  weight  to  be  of  a 
man  who  had  fasted  for  thirty-one  days.  The  greatest  loss  of  any 

983 


984  RECORDING  WEIGHT  AT  DEATH 

one  man  was  of  36  kilograms  (79  pounds),  or  50  per  cent.  Among 
the  number  there  were  24  cases  of  broncho-pneumonia,  and  their 
average  loss  of  weight  was  14  kilograms,  or  20  per  cent;  12  cases  of 
gunshot  wounds  with  sepsis,  showing  an  individual  loss  of  18  kilo- 
grams, or  27  per  cent;  7  cases  of  tuberculosis  with  a  loss  of  20 
kilograms,  or  29  per  cent;  and  5  cases  of  typhoid  fever  whose  average 
loss  amounted  to  2 1  kilograms,  or  30  per  cent. 

The  statistics  are  too  meager  to  warrant  far-reaching  con- 
clusions, but  they  illustrate  the  importance  of  body  weights  at 
death.  For  example,  take  pneumonia.  In  the  lobar  type  we  have 
been  taught,  on  the  one  hand,  by  von  Leyden  to  expect  a  retention 
of  weight  due  to  the  retention  of  sodium  chloride,  a  piece  of  work 
which  demands  confirmation,  while  more  recently  the  increased 
excretion  of  nitrogen  in  broncho-pneumonia,  found  by  the  inves- 
tigators at  Camp  Lee,  would  suggest  a  marked  loss  of  weight, 
because  each  30  grams  of  nitrogen  lost  above  the  intake  represent 
the  loss  of  I  kilogram  of  muscle  tissue.  Is  it  not  possible  that  different 
types  of  pneumonia  may  be  accompanied  by  variations  in  the  loss 
of  weight? 

The  cause  of  the  decrease  in  weight  at  death  varies.  Although 
the  percentage  loss  of  weight  may  be  the  same  in  fasting  as  in 
broncho-pneumonia,  who  would  assign  to  it  the  same  explanation? 
Obviously  the  loss  of  weight  in  dysentery  rests  upon  a  different 
basis  from  that  which  occurs  in  tuberculosis,  but  the  explanation 
may  not  be  as  simple  as  first  appears.  It  is  to  the  pathologist  in 
his  broadened  role  that  we  look  for  the  elucidation  of  such  problems, 
and  it  is  particularly  appropriate  that  he  undertake  the  task  now 
when  renewed  attention  is  being  devoted  to  studies  of  blood 
volume,  which  involve  great  changes  in  weight.  Is  the  loss  due  to 
water,  and  is  this  dependent  upon  salt  metabolism  or  simply  to 
variations  in  the  intake  or  outgo  of  water,  or  is  it  related  to  inroads 
upon  the  glycogen  reserve  or  the  destruction  of  protein  and  fat? 
How  do  these  percentage  losses  compare  with  those  which  take 
place  in  fasting?  The  answer  to  these  questions  will  foster  rational 
therapeusis  by  enabling  the  physician  to  adopt  specific  measures  for 
the  relief  of  these  pathological  states  during  life. 

Is  it  not  also  desirable  to  study  the  changes  in  weight  during 
the  early  days  following  operation? 


THE  TUMOR  IN  SYPHILIS  OF  THE  LIVER 
By  Thomas  McCrae,  M.D.,  F.R.C.P.  (Lontd.) 

Professor  of  Medicine,  Jefferson  Medical  College 

MY  special  interest  in  the  subject  of  syphilis  of  the  liver  goes 
back  to  the  days  when  I  was  a  resident  house  officer  in 
charge  of  the  private  wards  in  the  Johns  Hopkins  Hospital. 
One  day  Sir  William  Osier  said  to  me  that  there  was  a  patient  with  an 
interesting  abdominal  tumor  coming  into  the  private  ward,  and 
asked  me  to  examine  him  and  make  a  diagnosis  if  I  could.  The  pa- 
tient was  a  very  depressed  individual,  who  promptly  volunteered 
the  information  that  he  had  carcinoma  of  the  stomach  and  had 
been  told  that  a  radical  operation  might  be  possible,  but  that  in  any 
case  an  exploration  should  be  done  immediately.  He  had  consulted 
Sir  William  Osier,  hoping  that  he  might  have  some  other  suggestion 
to  make.  The  patient  was  quite  emaciated,  had  a  well-marked 
secondary  anemia  with  a  slight  grade  of  jaundice,  and  showed  a 
very  definite  tumor  mass  in  the  epigastrium.  As  a  result  of  my 
examination  I  felt  very  doubtful  of  the  diagnosis  of  carcinoma  of 
the  stomach,  but  I  had  no  definite  idea  as  to  what  the  condition 
actually  was.  Sir  William  Osier's  diagnosis  was  syphilis  of  the  liver, 
the  correctness  of  which  was  proved  by  the  outcome.  Under  sp)ecific 
treatment  the  tumor  disappeared  with  great  rapidity  and  the 
patient  gained  rapidly  in  every  way.  He  soon  regained  excellent 
health  and  has  remained  well  from  that  time  to  the  present. 

The  result  in  this  patient  illustrates  one  of  the  reasons  why  a 
more  complete  knowledge  of  syphilis  of  the  liver  is  impKjrtant.  But 
for  a  correct  diagnosis  this  patient  would  have  had  an  abdominal 
section  done,  which  would  have  been  quite  unnecessary.  It  is  no 
uncommon  thing  to  see  patients  with  syphilis  of  the  liver  on  whom 
an  abdominal  section  has  been  performed,  the  diagnosis  not  always 
being  made  even  after  the  abdomen  has  been  opened. 

The  whole  question  of  syphilis  of  the  liver  has  been  curiously 
neglected,  and  it  is  not  strange  that  there  is  so  little  recognition 

985 


986       THE  TUMOR  IN  SYPHILIS  OF  THE  LIVER 

of  the  character  of  the  tumor  to  which  it  gives  rise.  In  the  majority 
of  cases  there  is  either  marked  enlargement  of  the  Hver  or  a  tumor 
mass  of  some  kind  is  present.  Thus  in  the  85  cases  studied  in  this 
series  only  5  were  an  exception  to  this.  One  general  point  is  of  par- 
ticular interest  and  importance — this  is  the  relatively  greater  in- 
volvement of  the  left  lobe  as  compared  with  the  right,  a  condition 
so  marked  that  it  should  always  excite  suspicion  of  syphihs.  This 
involvement  of  the  left  lobe  was  found  in  48  cases  of  this  series. 

In  a  previous  communication^  I  described  the  changes  in  the  liver 
under  three  headings,  and  further  experience  has  shown  that  these 
include  the  great  majority  of  the  cases.  The  forms  are: 
(i)  General  enlargement  of  the  liver; 

(2)  Nodular  masses; 

(3)  A  rounded  tumor. 

It  must  be  remembered  that  the  stage  at  which  the  patient  is  ex- 
amined must  influence  the  occurrence  of  a  tumor  mass.  The  tendency 
is  to  cicatrization,  and  hence  in  late  stages  there  may  be  marked 
deformity — with  which  the  pathologist  is  usually  more  familiar 
than  the  clinician — or  a  cirrhotic  process  with  notable  contracture. 
But  despite  this  tendency  to  the  formation  of  scar  tissue  the  liver 
may  show  enlargement  or  masses  for  a  long  period — in  fact,  it  is 
difficult  to  set  hmits  to  the  time.  Some  patients  give  definite  histories 
of  the  tumor  or  the  enlarged  liver  having  been  recognized  many 
years  before.  This  persistence  of  the  enlargement  for  a  long  period 
is  a  striking  feature. 

Several  other  abdominal  features  are  worthy  of  mention  in  asso- 
ciation with  a  special  discussion  of  the  tumor.  Among  the  symptoms 
pain  is  a  common  complaint,  often  severe,  marked  tenderness  accom- 
panying it  frequently.  Ascites  had  occurred  or  was  present  in  38 
of  the  85  cases,  and  both  the  duration  and  variabihty  of  this  are 
striking.  One  patient  had  ascites  at  intervals  over  a  period  of  eleven 
years,  in  which  time  tapping  had  been  done  seventeen  times.  The 
history  of  ascites  which  has  been  intermittent  is  particularly  sug- 
gestive. Splenic  enlargement  is  another  frequent  finding  and  was 
present  in  54  of  the  cases.  In  the  majority  the  increase  in  size  is  very 
marked,  and  this  is  a  frequent  cause  of  error,  as  the  diagnosis  of 
splenic  anemia  is  made. 

*  Am.  Jour.  Med.  Sc,  1912,  CXLIV,  625. 


I 


THE  TUMOR  IN  SYPHILIS  OF  THE  LIVER        987 

The  various  forms  of  change  in  the  liver  may  be  discussed  in  detail* 

(i)  General  Enlargement.  This  was  the  most  frequent  form  and 
was  found  in  39  cases.  The  extent  of  enlargement  varies  from  a 
liver  the  edge  of  which  is  perhaps  2  inches  below  the  costal  margin 
to  one  which  reaches  below  the  level  of  the  navel — an  average 
increase  being  shown  by  finding  the  edge  3  or  4  inches  below  the 
costal  margin  in  the  right  nipple  line.  The  liver  is  usually  hard,  with 
a  firm,  rounded  edge,  and,  as  a  rule,  the  left  lobe  shows  relatively  a 
greater  increase  in  size  than  the  right.  Sometimes  the  left  lobe  pre- 
sents a  large  rounded  prominence  in  the  epigastrium.  In  a  few  cases 
the  surface  may  be  slightly  irregular,  and  occasionally  there  are  well- 
marked  fissures.  In  nearly  all  the  cases  of  this  group  the  liver  is 
tender  on  palpation.  In  15  cases  there  was  distention  of  the  surface 
veins  and  in  17  ascites  was  present. 

It  is  easy  to  see  how  mistakes  in  diagnosis  may  arise.  With  an 
enlarged,  tender  liver,  fever,  and  perhaps  chills  and  sweats,  a  diag- 
nosis of  abscess  of  the  liver  may  be  made,  while  if  there  is  cardiac 
disease  with  loss  of  compensation,  the  liver  changes  may  be  regarded 
as  due  to  chronic  passive  congestion.  But  the  most  frequent  error 
is  to  regard  the  condition  as  ordinary  portal  cirrhosis  with  enlarge- 
ment. The  mistake  is  the  more  easily  made  by  reason  of  the  occur- 
rence of  dilated  surface  veins  and  ascites.  There  are  several  features 
which  are  worthy  of  note.  One  is  the  persistence  of  the  tumor.  Such 
an  enlargement  may  persist  for  years  and  be  associated  with  ascites, 
which  may  increase  and  decrease.  Some  of  the  patients  had  been 
tapped  at  intervals  over  a  period  of  years,  which  is  quite  contrary 
to  the  course  of  ordinary  hepatic  cirrhosis. 

(2)  Nodular  Masses.  These  may  occur  practically  in  any  part 
of  the  liver,  but  most  often  are  found  in  the  epigastrium  or  the 
adjoining  right  hypochondrium.  In  a  certain  number  of  cases  they 
may  be  found  over  every  part  of  the  liver  that  is  palpable.  They 
usually  occur  in  a  liver  which  shows  some  general  enlargement,  but, 
as  a  rule,  this  is  not  as  marked  as  in  the  first  group.  There  were  21 
cases  of  this  form.  Ascites  occurred  in  10  cases  and  prominence  of 
the  surface  veins  was  marked  in  8  cases.  One  p)oint  of  some  interest 
is  the  occurrence  of  a  friction  rub  over  these  nodules.  This  was 
noted  in  a  few  instances  and  should  always  be  kept  in  mind  and 
looked  for. 


988        THE  TUMOR  IN  SYPHILIS  OF  THE  LIVER 

When  one  considers  the  many  general  symptoms  that  occur 
with  syphilis  of  the  liver,  the  possibilities  of  incorrect  diagnosis 
in  this  form  are  very  evident.  With  the  loss  in  weight  and  marked 
anemia,  the  most  likely  mistake  is  to  diagnose  the  condition  as 
carcinoma.  This  diagnosis  was  made  in  several  of  the  cases,  in 
some  of  which  it  was  only  the  lapse  of  time  which  proved  it  to 
be  incorrect.  In  several  others  which  I  have  seen  an  exploration 
had  been  done,  the  nodule  being  regarded  as  a  tumor  about  the 
pylorus.  Another  possible  error  is  to  consider  the  enlargement  as 
due  to  tuberculous  peritonitis,  the  nodules  in  the  epigastrium 
being  regarded  as  representing  an  irregularly  thickened  omentum. 
The  occurrence  of  ascites  might  easily  increase  the  likelihood  of 
this  diagnosis. 

There  is  one  finding  which  should  help  to  prevent  error,  and  that 
is  the  enlargement  of  the  spleen,  which  occurs  so  frequently  with 
syphilis  of  the  liver,  and  so  rarely  with  such  conditions  as  neoplasm 
and  tuberculous  peritonitis  that  it  should  be  a  safeguard  against 
error.  Unless  a  complete  examination  is  made,  however,  the  splenic 
enlargement  may  be  missed  entirely,  especially  if  ascites  is  present. 
The  enlargement  of  the  left  lobe  of  the  liver  being  relatively  greater 
than  that  of  the  right  was  generally  manifested  in  this  group,  and 
is  another  aid  against  error. 

(3)  Rounded  Tumor.  This  was  found  in  17  cases,  and  may  be 
associated  with  general  enlargement,  but  the  most  striking  form  is  the 
large,  smooth,  rounded  projection  which  is  most  likely  to  be  found 
in  the  epigastrium.  In  some  cases  this  was  so  marked  that  a  large 
prominence  was  visible.  In  no  instance  were  nodular  masses  found 
with  this  form,  the  surface  being  smooth;  but  occasionally  a  friction 
rub  was  heard  over  the  mass.  I  have  a  very  distinct  recollection  of 
the  first  case  of  this  form  which  came  under  my  observation.  Nearly 
every  man  who  examined  it  had  a  different  suggestion;  after  the 
abdomen  was  opened  the  surgeon  could  not  make  a  diagnosis;  and 
the  pathologist  who  examined  a  portion  removed  at  operation  could 
only  say  that  there  was  some  increase  of  the  interstitial  tissue.  It 
is  evident  that  with  fever  and  possibly  chills  a  diagnosis  of  abscess 
might  easily  be  made;  in  general,  however,  the  condition  is  usually 
regarded  as  a  massive  neoplasm.  Only  the  passage  of  years  may  cor- 
rect this,  and  then  valuable  time  has  been  lost  and  the  disease  may 


THE  TUMOR  IN  SYPHILIS  OF  THE  LIVER        989 

be  beyond  help.  Ascites  was  present  in  10  cases  and  an  enlarged 
spleen  in  the  same  number. 

(4)  In  a  few  instances  the  cases  do  not  fall  exactly  into  any  of  the 
preceding  groups.  If  the  condition  has  existed  for  some  time  and  much 
fibroid  change  with  shrinking  has  occurred,  there  may  be  no  enlarge- 
ment, and  the  irregular,  hard  left  lobe  may  be  felt  in  the  epigastrium. 
It  may  not  be  possible  to  feel  the  edge  of  the  liver  in  the  right  nip- 
ple line.  Again,  there  may  be  a  continuation  of  a  nodular  mass  with 
marked  irregularity  of  the  left  lobe.  In  general,  it  may  be  said  that 
the  changes  usually  come  under  one  of  the  three  forms  described. 

Errors  in  Diagnosis.  These  are  discussed  here  only  in  so  far  as 
they  result  from  the  finding  of  nodular  or  rounded  masses  or  the 
recognition  of  an  enlarged  liver.  The  errors  are  in  one  of  two  groups: 
(i)  It  is  recognized  that  there  is  some  diseased  condition  of  the  liver 
or  gall  bladder,  but  the  nature  of  this  is  not  diagnosed,  or  (2)  the 
primary  condition  in  the  liver  is  not  recognized,  and  is  regarded  as 
due  to  disease  elsewhere.  The  result  of  error  may  always  be  serious 
in  that  a  condition  which  usually  yields  to  treatment  is  not  recog- 
nized and  time  is  given  for  further  damage,  while  a  further  p>ossi- 
bility  is  that  an  unjustified  operation  is  done,  both  results  fairly 
common  in  my  experience.  The  delay  in  proper  treatment  may  re- 
sult in  death,  as  shown  by  a  case  which  was  very  striking,  in  which 
the  patient  died  in  three  days  after  admission,  and  at  autopsy  it  was 
found  that  the  process  had  caused  obliteration  of  the  inferior  vena 
cava  and  hepatic  vein,  with  resulting  thrombosis.  The  errors  in  diag- 
nosis for  which  laparotomy  is  done  are  various.  In  some  the  condition 
was  regarded  as  being  cholelithiasis  or  cholecystitis,  in  others  car- 
cinoma, cyst,  or  abscess  of  the  liver,  or  tuberculous  peritonitis. 
Probably  the  most  common  error  is  to  regard  the  case  as  one  of 
ordinary  cirrhosis  with  enlargement,  the  reason  for  which  is  very 
evident.  A  knowledge  of  the  manifestations  of  syphilis  of  the  liver 
is  the  greatest  safeguard. 

An  error  which  had  been  made  in  several  cases  of  this  series  was 
to  regard  them  as  splenic  anemia.  Naturally  this  occurred  when  the 
spleen  was  markedly  enlarged,  and  the  mistake  was  probably  made 
because  syphihs  was  not  considered.  It  should  be  remembered  that 
syphiHs  may  cause  a  marked  enlargement  of  the  spleen.  The  point 
may  be  raised  as  to  whether  the  fiver  is  enlarged  in  splenic  anemia. 


990        THE  TUMOR  IN  SYPHILIS  OF  THE  LIVER 

My  view  is  that  this  is  unusual,  and  a  marked  increase  in  size 
should  certainly  arouse  suspicion  as  to  the  correctness  of  such  a 
diagnosis.  The  possibility  of  confusion  from  amyloid  disease  or  an 
unusual  form  of  Hodgkin's  disease  does  not  seem  probable. 

Congenital  Svpbilis.  In  all  the  cases  of  late  congenital  syphilis 
of  the  liver  which  have  been  recognized  the  tumor  has  been  of  the 
third  form,  that  is,  a  large,  rounded  mass  on  a  generally  enlarged 
liver.  As  the  age  of  occurrence  is  in  childhood  or  youth,  the  condition 
is  puzzling  unless  syphilis  is  considered.  There  were  5  such  cases  in 
the  series. 


I 


SPLENIC  ANEMIA 
By  W.  J.  Mayo,  M.D.,  Rochester,  Minn. 

THE  scientific  vassalage  of  America  to  the  Teutonic  educational 
system  has  been  the  outstanding  feature  of  American  medi- 
cine for  the  last  generation.  The  chief  characteristic  of  this 
system,  the  delineation  of  minute  details  at  the  expense  of  perspec- 
tive, has  resulted  in  a  loss  of  the  sense  of  proportion  in  estimating 
the  comparative  values  of  the  important  and  the  unimportant 
manifestations  of  disease.  The  German  method  resulted  in  the 
accumulation  of  a  mass  of  scientific  facts,  but  it  did  not  develop 
a  well-devised  system  of  accounting  by  which  the  more  significant 
features  of  disease  could  properly  be  brought  into  prominence. 
Clinical  medicine  to-day  is  turning  toward  what  might  be  called 
the  British  conception,  by  which  a  perspective  of  the  disease  is 
first  obtained;  that  is,  the  disease  is  viewed  as  a  whole,  while  em- 
phasis is  given  to  various  characteristics  according  to  their  impor- 
tance, and  the  patient  rather  than  the  collection  of  data  is  made 
the  chief  object  of  interest. 

The  name  of  Sir  William  Osier  stands  out  pre-eminently  among 
the  men  who  have  striven  for  a  rational  development  of  clinical 
medicine  based  on  the  central  idea  of  curing  the  patient.  Twenty 
years  ago  my  attention  was  first  called  to  splenic  anemia  by  Osier's 
remarkable  paper  on  this  subject.  His  report  of  cases  and  his 
critical  remarks,  exhibiting  a  fine  example  of  his  clinical  acumen, 
are  still  the  best  exposition  in  literature  of  the  fundamental  charac- 
teristics of  splenic  anemia,  and  definitely  establish  this  name  for 
a  condition  which  for  many  years  previously  had  been  described 
under  various  titles. 

Splenic  anemia,  as  Osier  pointed  out,  is  a  clinical  entity.  Its 
chief  characteristics  are  an  idiopathic  enlargement  of  the  spleen 
and  a  chronic  progressive  and  intercurrent  anemia  which  are  the 
antecedents  of  phenomena  related  to  portal  circulatory  obstruction, 
such  as  gastro-intestinal  hemorrhage  and  ascites  which  eventually 

991 


992  SPLENIC  ANEMIA 

cause  death.  If  an  attempt  is  made  to  study  the  clinical  picture 
of  splenic  anemia  in  its  minutife,  it  will  be  found  that  the  picture 
fades  quickly  away,  since  its  etiology  is  obscure  and  pathologically 
it  presents  no  distinctive  characteristics;  only  when  it  is  seen  as  a 
whole  and  by  exclusion  is  a  diagnosis  possible. 

In  1866  Gretsel,  in  Griesinger's  clinic,  reported  a  case  of  splenic 
anemia  in  a  child,  and  Griesinger,  who  termed  the  condition  anemia 
splenica,  had  many  such  cases  in  adults.  In  1871  H.  C.  Wood  wrote 
on  the  subject;  in  1885  Osier  differentiated  it  in  a  discussion  of 
the  differential  diagnosis  of  leukemia  and  pernicious  anemia,  and 
in  1899  Sippy  made  a  critical  summary  of  the  literature.  Since 
the  publication  of  Osier's  article  in  1900  the  principal  advances  in 
the  investigation  of  the  disease  have  been  made  in  connection 
with  the  recognition  of  those  conditions  which,  though  they  simulate 
splenic  anemia,  have  been  found  to  have  a  specific  etiology.  Hemo- 
lytic icterus,  in  which  the  jaundice  was  slight  and  intermittent, 
had  been  confused  with  splenic  anemia.  Occasional  cases  of  per- 
nicious anemia,  in  which  the  spleen  was  greatly  enlarged,  had  also 
been  thus  improperly  classified,  not  because  the  resemblance 
was  striking,  but  because  an  enlarged  spleen  and  the  anemia  were 
looked  on  as  characteristic  of  the  disease,  and  further  investigation 
for  the  purpose  of  making  a  correct  diagnosis  was  not  continued. 
The  splenomegalia  of  syphilis  has  also  come  to  be  recognized,  and 
the  enlarged  spleen  of  chronic  malaria,  chronic  sepsis,  tuberculosis, 
and  Gaucher's  disease  have  been  removed  from  the  splenic  anemia 
group  as  characteristic  diagnostic  features  have  developed.  Various 
competent  observers  believe  that  von  Jaksch's  disease  (infantile 
pseudoleukemia)  is  the  infantile  form  of  splenic  anemia,  in  which 
the  presence  of  a  leukocytosis  and  abnormal  marrow  cells  may  be 
explained  by  the  transitional  characteristics  of  infants*  blood 
(Giffin).  Von  Jaksch's  disease  is  probably  a  syndrome  produced 
by  various  infantile  disorders.  There  still  remains,  however,  an 
irreducible  number  of  cases  which  present  the  clinical  picture  of 
splenic  anemia  and  have  an  unknown  etiology. 

The  chief  pathological  condition  found  in  the  spleen  in  splenic 
anemia  is  a  generalized  fibrosis.  Deposits  of  connective  tissue, 
compression  atrophy  of  the  malpighian  corpuscles,  and  endophlebitis 
are  the  main  features,  and  these  are  not  grossly  different  from  those 


SPLENIC  ANEMIA  993 

ot  the  splenomegalia  of  syphilis,  malaria,  and  other  diseases  of 
known  origin  associated  with  fibrotic  spleens.  The  spleen  of  splenic 
anemia  has  been  studied  more  carefully  post-mortem,  and  this, 
I  believe,  has  given  rise  to  some  misunderstanding  of  the  condition 
of  the  organ  when  removed  in  the  earlier  stages  of  the  disease. 

Warthin  and  Dock  have  called  attention  to  the  importance  of 
thrombosis  of  the  splenic  portal  and  mesenteric  veins  which  have 
been  found  post-mortem.  They  believe  that  this  condition  is  re- 
sp>onsibIe  for  the  ascites  that  occurs  in  some  of  these  cases.  Warthin 
showed,  however,  that  ligation  of  the  splenic  vein  produced  atrophy 
and  not  enlargement  of  the  spleen.  In  three  cases  in  our  experience 
in  which  death  followed  splenectomy  for  splenic  anemia,  marked 
ascites  was  present,  while  thrombosis  of  the  superior  mesenteric 
and  portal  vessels  caused  death.  In  one  instance  the  thrombosis 
must  have  been  of  many  months*  or  years'  duration,  as  the  patient 
had  been  ill  for  ten  years  and  had  had  ascites  for  two  years;  the 
operation  had  been  done  in  the  last  stages  of  exhaustion.  Comp>en- 
satory  circulation  in  this  case  had  been  established  through  an 
extensive  anastomosis  about  the  occluded  superior  mesenteric 
vessels.  The  pathological  change  in  the  occluded  vessels  was  of 
enormous  extent,  with  the  organization,  apparently,  of  a  clot  that 
had  become  canalized,  the  final  catastrophe  completely  blocking 
the  circulation  with  fresh  thrombi.  There  were  no  changes  in  the 
liver  in  this  case,  but  in  the  other  two  cirrhotic  changes  were  well 
marked. 

Fibrotic  Splenomegalia.  An  interesting  feature  of  the  con- 
ception of  splenic  anemia  is  the  quite  obvious  attempt  to  split  oflF 
from  the  disease  all  of  those  conditions  in  which  the  etiological  factor 
is  known,  but  which  are  otherwise  characteristic.  Unless  gumma  or 
the  spirochete  itself  is  found  in  the  spleen,  there  is  little  about  the 
fibrosis  and  vascular  changes  of  syphilitic  splenomegalia  to  dis- 
tinguish it  from  the  splenomegalia  of  splenic  anemia;  the  anemia  is 
quite  the  same.  We  have  removed  an  enlarged  spleen  in  chronic 
syphilis  in  five  instances  in  which,  by  the  most  careful  and  prolonged 
treatment,  we  had  been  unable  to  cure  the  patient  of  syphilis  or  to 
reduce  the  splenomegalia  to  relieve  the  anemia;  after  the  spleen 
was  removed  the  patients  were  quickly  cured.  In  three  of  these 
cases  gumma  was  found  in  the  liver  at  the  time  the  spleen  was 


994  SPLENIC  ANEMIA 

removed.  Following  the  splenectomy  antiluetic  treatment  proved  to 
be  much  more  effective,  the  liver  became  normal,  and  the  patients 
have  remained  well  for  various  periods  up  to  five  years  (Giffm).  The 
experience  of  Jonnesco  in  removing  the  spleen  in  the  splenomegalias 
of  chronic  malaria  and  thereby  promptly  curing  the  patient  of  both 
the  malaria  and  anemia  again  illustrates  the  therapeutic  value  of 
splenectomy. 

The  foregoing  results  lead  to  the  belief  that  splenic  anemia  is  a 
clinical  entity,  even  when  the  cause  is  known,  and  that  fibrotic 
splenomegalia  produces  anemia,  irrespective  of  the  initial  cause  of 
splenic  enlargement.  I  am  much  in  sympathy  with  this  view.  A 
patient  with  chronic  splenomegalia  who  presents  characteristics  of 
chronic  secondary  anemia  but  who  is  not  relieved  by  treatment  is 
potentially  a  sufferer  from  splenic  anemia,  and  will  probably  be 
cured  by  splenectomy  without  regard  to  the  cause  of  the  disease. 
This  conclusion  throws  the  burden  of  the  production  of  chronic 
anemia  on  the  spleen,  while  knowledge  of  the  cause  is  unessential 
and  may  be  even  misleading,  unless  it  leads  to  corrective  treatment 
and  renders  eligible  for  surgical  consideration  any  and  all  enlarge- 
ments of  the  spleen  in  which  anemia  is  the  chief  symptom.  The 
anemia  in  the  earlier  stages  may  not  be  severe  or  continuous,  the 
enlarged  spleen  may  exist  for  months  or  years  without  anemia, 
but  eventually  the  anemia  becomes  progressive  and  the  secondary 
complications  lead  to  death. 

The  Relation  oj  Splenic  Anemia  to  BantVs  Disease.  In  1883 
Banti  described  a  splenomegalia  with  chronic  anemia  associated  with 
cirrhosis  of  the  liver.  In  numerous  communications  since  his  original 
paper,  Banti  has  added  various  diagnostic  criteria  which  have  still 
further  obscured  rather  than  clarified  the  subject.  However,  these 
criteria  have  made  it  possible  to  designate  as  Banti*s  disease  almost 
any  form  of  splenomegalia  accompanied  by  anemia  and  hver 
changes  in  which  a  definite  etiology  cannot  be  established.  Mos- 
chowitz,  in  a  critical  analysis  of  Banti's  disease,  came  to  the  con- 
clusion, with  which  I  think  nearly  all  observers  will  agree,  that 
Banti's  disease  cannot  be  distinguished  from  splenic  anemia,  and 
that  what  is  ordinarily  called  Banti's  disease  is  a  terminal  stage 
which  may  be  found  in  some  cases  of  splenic  anemia.  That  many 
patients  die  from  splenic  anemia  without  Hver  changes  is  certain. 


SPLENIC  ANEMIA  995 

That  some  patients  have  cirrhosis  of  the  liver  at  an  early  stage  of 
splenic  anemia  is  equally  certain.  Some  clinicians  believe  that  all 
those  conditions  called  splenic  anemia  in  which  cirrhosis  of  the 
liver  is  a  prominent  feature,  are  cases  of  primary  cirrhosis  of  the 
liver,  just  as  a  still  larger  group  of  clinicians  believe  that  cirrhosis 
of  the  liver  is  merely  a  terminal  phase  of  splenic  anemia.  Personally, 
I  have  often  been  unable  to  determine  in  a  given  case  of  spleno- 
megalia  with  cirrhosis  of  the  liver  and  ascites  whether  the  condition 
was  primary  in  the  liver  or  in  the  spleen.  We  are  often  forced  to 
rely  on  the  very  indefinite  history  as  to  which  was  discovered  first — 
the  condition  of  the  spleen  or  of  the  liver.  Such  data  are,  of  course, 
wholly  unreliable.  ♦  "  >  i . 

The  spleen  as  normally  situated  in  the  average  person  must  be 
nearly  twice  its  normal  size  in  order  to  be  palpable,  and  the  enlarge- 
ment cannot,  therefore,  be  definitely  established  until  it  reaches  a 
weight  of  300  or  400  grams,  if  we  accept  Sappey's  estimate  of  195 
grams  as  the  weight  of  the  normal  spleen.  It  should  be  borne  in 
mind  that  considerable  latitude  must  be  permitted  in  estimating 
the  size  of  the  spleen;  percussion  to  determine  its  size  has,  I  believe, 
but  little  value.  I  have  seldom  found  that  the  area  defining  the  size 
and  exact  location  of  the  spleen,  marked  out  in  advance  by  per- 
cussion, was  corroborated  by  inspection  after  the  abdomen  was 
opened.  And  this  is  to  a  lesser  degree  true  of  our  methods  of  ascer- 
taining the  size  and  condition  of  the  liver,  unless  it  can  be  palpated 
below  the  margin  of  the  ribs.  Therefore  early  diagnosis  of  the  phys- 
ical condition  of  the  spleen  and  liver  presents  uncertainties  which 
must  be  recognized. 

Ascites,  without  changes  in  the  liver,  occurs  in  splenic  anemia. 
The  mere  presence,  therefore,  of  an  ascites  in  connection  with  spleno- 
megalia  is  not  sufficient  to  demonstrate  that  the  liver  is  at  fault, 
although  I  believe  it  may  be  said  that  anemia  is  not  a  marked  feature 
of  primary  cirrhosis  of  the  liver  even  when  ascites  is  present,  while 
in  splenic  anemia  it  is  an  early  and  more  or  less  continuous  mani- 
festation. It  seems  probable  that  certain  as  yet  unidentified  toxic 
agents  strained  out  of  the  blood  by  the  spleen  are  responsible  for 
the  fibrosis  of  the  spleen  and  also  for  the  cirrhosis  of  the  liver. 

Without  going  into  the  question  of  the  physiology  of  the  spleen, 
concerning  which  little  is  known,  one  may  at  least  say  that  the  frag- 


996  SPLENIC  ANEMIA 

mentation  of  worn-out  red  corpuscles  is  one  of  the  spleen's  functions 
and  that  when  fibrotic  it  destroys  an  excessive  number  of  red  cor- 
puscles, and  this  without  regard  to  the  etiology  of  the  fibrosis, 
but  probably  does  not  interfere  directly  with  blood  production.  The 
anemia  is  doubtless  a  "habit-anemia"  (Rous)  and  simply  an  evi- 
dence of  the  gradual  adaptation  of  the  organism  to  a  lower  level  of 
blood  maintenance.  The  bone  marrow  is  not  markedly  stimulated 
to  overproduction,  nor  is  there  evidence  of  the  toxic  irritation  of 
the  bone  marrow  so  characteristic  of  the  so-called  hemolytic  ane- 
mias. Moreover,  it  may  be  that  the  pathologic  changes  of  the  disease 
actually  reduce  pigment  production,  which  seems  to  be  an  imp>ortant 
function  of  the  Hver,  and  in  this  way  reduce  the  hemoglobin  balance 
and  foster  the  anemia. 

It  it  also  known  that  the  spleen  acts  as  a  filter,  removing  bacteria 
from  the  blood  stream,  as  in  typhoid  and  tuberculosis;  protozoa, 
as  in  syphilis  and  malaria,  and  undoubtedly  other  noxious  agents. 
The  spleen,  unable  to  destroy  these  various  substances,  sends 
them  through  the  splenic  vein  to  the  liver  for  destruction,  and  the 
reaction  of  the  liver  to  chronic  irritants  is  in  the  nature  of  a  connect- 
ive tissue  disease  which  we  speak  of  as  cirrhosis  without  regard  to 
its  cause.  If  the  spleen  is  unable  to  rid  itself  of  all  the  material 
that  it  filters  out  of  the  blood  stream  sequestration  of  the  filtrates 
may  occur  and  give  rise  to  the  various  splenomegalias  with  assured 
etiology,  such  as  those  due  to  the  spirochete,  plasmodium,  typhoid 
bacillus,  tuberculosis  bacillus,  and  to  others  which  have  as  yet  no 
known  etiology. 

The  spleen  has  diflferentiated  and  characteristic  cells.  It  is  there- 
fore capable  of  varied  pathological  conditions.  The  liver  has  but  one 
typ>e  of  cells  with  diflFerent  physiological  activity,  and  its  processes 
are  less  varied.  The  reaction  of  the  liver  to  chronic  irritation, 
reaching  it  by  way  of  the  jjortal  system  without  regard  to  cause, 
is  usually  a  fibrosis  which  we  call  portal  cirrhosis. 

The  p>ortaI  cirrhosis  of  Laennec  does  not  vary  in  type,  whether 
produced  by  gin  or  pepper,  or  whether  it  is  found  locally  about 
areas  of  tuberculosis,  gumma,  or  cancer.  Usually  we  have  diagnosed 
cirrhosis  with  the  hob-nail  variety  of  Laennec  in  mind.  Yet  in  our 
experience,  accepting  fifty-five  ounces  as  the  weight  of  the  average 
liver,  the  cirrhotic  liver  is  as  often  enlarged  as  it  is  contracted. 


SPLENIC  ANEMIA  997 

As  pointed  out  by  Osier,  the  beer  drinker  and  others  may  have 
huge,  smooth,  cirrhotic  livers,  in  which  the  characteristic  fibrosis  is 
smoothed  out  by  deposits  of  fat.  On  this  assumption,  therefore, 
we  could  say  inferentially  that  the  variety  of  splenic  anemia  which 
is  accompanied  by  cirrhosis  of  the  liver  and  has  been  called  Banti's 
disease  is  a  condition  in  which  the  fibrosis  of  the  spleen  and  the 
fibrosis  of  the  Hver  are  due  to  the  same  agent,  that  they  have  a 
common  etiology,  and  that  the  removal  of  the  spleen  when  the 
disease  is  not  too  far  advanced,  cures  the  anemia  by  eliminating 
excessive  blood  destruction  and  relieves  the  liver  of  such  substances 
as  have  been  filtered  from  the  blood  stream  so  that  the  cirrhotic 
process  in  the  liver  itself  is  checked  and  the  ascites  disappears. 
We  have  patients,  whose  cases  fulfilled  this  description,  alive  and 
in  good  health  for  years  following  splenectomy. 

I  have  previously  called  attention  to  the  fact  that  there  is 
another  element  of  relief  following  splenectomy  which  must  be 
taken  into  consideration.  In  the  normal  condition  30  per  cent  of 
all  the  blood  carried  to  the  liver  comes  through  the  splenic  vein, 
while  in  enormously  enlarged  spleens  the  splenic  vein  may  be  the 
size  of  the  p>ortaI  vein.  The  removal  of  the  spleen  in  these  cases 
reheves  the  liver  of  an  overload,  and  it  then  becomes  able  to  carry 
on  its  function  without  those  evidences  of  circulatory  obstructions 
that  result  in  ascites  and  hemorrhages.  Splenectomy  may,  therefore, 
be  looked  on  as  an  equivalent  to  the  establishment  of  an  Eck*s 
fistula  or  the  condition  we  attempt  to  bring  about  by  the  establish- 
ment of  collateral  circulation,  after  the  method  of  Talma,  Morrison, 
and  Drummond,  through  the  vascular  channels  of  Sappey,  a  con- 
dition described  by  Fagge  as  found  with  advanced  cirrhosis  in  some 
person  killed  by  accident  while  in  apparent  health. 

Splenectomy.  Splenectomy  is  the  only  curative  treatment  for 
splenic  anemia.  Radium  and  the  x-ray  have  no  such  therapeutic 
successes  as  they  have,  for  instance,  in  the  palliation  of  leukemia. 
Iron,  arsenic,  etc.,  may  be  and  undoubtedly  are  of  importance  in 
temporarily  overcoming  the  more  severe  grades  of  anemia,  and 
transfusion,  following  hemorrhages,  is  also  of  value.  In  the  later 
stages,  when  serious  circulatory  changes  such  as  endophlebitis, 
thrombosis,  etc.,  have  developed,  the  risk  of  operation  is  great 
and  the  prospect  of  cure  is  of  course  lessened.  But  even  with  these 


998  SPLENIC  ANEMIA 

terminal  conditions,  many  patients  have  recovered  their  health 
and  remained  well  for  years  following  splenectomy. 

Discomfort  and  pressure,  from  the  size  and  weight  of  the  spleen 
itself,  and  the  anemia  are  the  two  conditions  produced  by  the 
splenomegalia  direct.  It  is  self-evident  that  splenectomy  relieves  all 
those  physical  changes  produced  by  the  enlarged  spleen,  and  removes 
the  small  but  definite  risk  of  splenic  traumatism,  (splenic)  apoplexy, 
spontaneous  rupture,  and  cystic  degeneration.  The  enlarged  spleen 
therefore  has  a  certain  pathological  significance,  and  when  not  caused 
by  an  incurable  condition,  such  as  leukemia,  or  when  not  relieved 
by  appropriate  treatment  in  cases  ordinarily  considered  curable, 
other  things  being  equal,  it  should  be  removed.  The  clinical  course 
of  splenic  anemia  may  be  very  slow  and  the  anemia  may  not  be 
continuous  in  the  earlier  stages;  it  has  its  ups  and  downs,  and  often 
for  long  periods  of  time  the  blood  will  be  found  approximating  the 
normal.  I  have  known  persons,  especially  women,  with  enlarged 
spleens,  to  carry  them  for  years  without  apparent  symptoms,  but 
eventually  anemia  has  developed.  In  our  experience  after  the  re- 
moval of  the  spleen  the  anemia  rapidly  disappeared  and  the  blood 
returned  approximately  to  normal  and  so  remained  (Chabrol  and 
Benard). 

Two  conditions  not  so  characteristic  of  fibrotic  spleens  in  general 
but  which  are  often  associated  with  splenic  anemia  remain  to  be 
discussed,  that  is,  hemorrhages,  especially  from  the  stomach,  and 
ascites.  A  large  majority  of  sudden  and  unexplained  hemorrhages 
from  the  stomach  in  adult  persons  are  the  result  of  changes  in  the 
spleen  or  liver,  or  both,  and  the  type  of  disease  to  be  found  in  both 
the  spleen  and  the  liver  is  a  fibrosis,  more  typical  in  the  liver, 
because  the  liver  has  but  a  single  kind  of  ceil  and  therefore  has 
less  variation  of  pathology  than  the  spleen,  which  has  groups  of 
specialized  cells.  Balfour  has  written  most  interestingly  concerning 
the  relation  of  the  spleen  to  unexplained  gastric  hemorrhages,  and 
has  reported  a  remarkable  case  in  which  splenectomy  restored 
to  health  a  patient  in  the  last  stages  of  exhaustion  from  repeated 
hemorrhages  extending  over  years.  It  is  true  that  cases  have  been 
noted  in  which  hemorrhages  from  the  stomach  have  recurred  after 
splenectomy,  but  in  the  majority  of  such  cases  hemorrhages  do  not 
recur. 


SPLENIC  ANEMIA  999 

For  reasons  that  I  have  already  pointed  out  the  changes  in  the 
spleen,  while  of  the  same  general  nature  as  those  in  the  liver,  do  not 
follow  a  specific  and  distinctive  course  similar  to  portal  cirrhosis  of  the 
liver.  The  blood  vessels  in  the  spleen  normally  lose  their  middle  and 
outer  coats,  and  the  blood,  except  for  the  endothelial  coating  of  the 
blood  vessels,  comes  in  direct  contact  with  the  splenic  pulp.  We 
find,  therefore,  much  greater  changes  in  the  blood  vessels  themselves 
than  are  found  in  the  vessels  of  the  portal  circulation  in  hepatic 
cirrhosis.  The  patient  with  cirrhosis  of  the  liver  often  has  gastric 
hemorrhages  and  ascites,  and  usually  comes  to  his  death  through 
portal  circulatory  obstructions.  This  is  also  true  of  the  patient  with 
splenic  anemia,  although  the  spleen  in  addition  causes  an  anemia 
peculiar  to  itself.  Forty  per  cent  of  the  blood  from  the  splenic 
artery  goes  to  the  stomach,  being  distributed  largely  about  the 
fundus,  and  hemorrhages  from  the  stomach  may  be  due  to  some 
specific  pK)ison  producing  the  gastric  erosions  of  Dieulafoy,  or  more 
probably  they  are  due  to  obstructed  portal  circulation  producing 
definite  back-pressure  on  gastric  vessels  distended  through  their 
strength.  Removal  of  the  spleen  in  this  type  of  case  may  act  by 
checking  the  distribution  of  toxic  material  or  by  reduction  of  the 
portal  circulation,  which  forces  the  blood  to  travel  around  extra- 
hepatic  channels  directly  into  the  general  circulation.  This  applies 
equally  to  the  ascites,  which  again  is  only  another  manifestation 
of  the  obstructed  portal  circulation. 

The  changes  found  at  necropsy  after  death  from  splenic  anemia 
are  not  necessarily  to  be  considered  the  conditions  that  exist  through- 
out the  whole  course  of  the  disease;  they  are  to  a  large  extent 
terminal.  Of  61  patients  with  splenic  anemia  from  whom  we  re- 
moved the  spleen  7  (11.7  per  cent)  died,^  3  from  thrombosis  of  the 
superior  mesenteric  and  portal  veins,  an  acute  condition  superim- 
f>osed  on  a  previous  canalized  thrombosis  having  its  seat  in  the 
splenic  vein.  These  cases  reproduced  the  picture  seen  at  necropsy  in 
the  unoperated  patient.  All  the  patients  operated  on  who  were  not 
in  an  advanced  stage  of  the  disease  recovered  and  have  remained 
well.  We  must  therefore  look  on  ascites,  edema  of  the  lower  extremi- 
ties, and  cardio-renal  decompensation  as  terminal  conditions  which 

J  These  statistics  extend  to  December  31,  1918,  and  include  as  operative  deaths  all 
patients  dying  in  the  hospital,  without  regard  to  cause  of  death  or  length  of  time  after 
operation. 


1000  SPLENIC  ANEMIA 

increase  the  dangers  of  operation.  Yet  the  spleen  may  be  removed 
successfully  even  in  the  terminal  stage  of  the  disease.  We  have  oper- 
ated on  a  number  of  patients  for  splenic  anemia  who  had  extensive 
cirrhosis  of  the  liver,  two  of  the  Laennec  tyf>e.  Following  splenec- 
tomy the  ascites  disappeared  and  the  hemorrhages  from  the  stomach 
stopped;  all  who  recovered  from  the  operation  are  ahve  and  appar- 
ently well  after  some  years.  The  spleens  in  cases  of  splenic  anemia 
are  usually  adherent  and  difficult  to  remove,  and  in  the  late  cases 
when  endophlebitis  and  thrombosis  are  marked  the  danger  of  an 
acute  thrombosis  of  the  large  vessels  of  portal  circulation  is  great. 
Eliminating  the  advanced  cases  the  mortality  from  splenectomy  for 
splenic  anemia  has  been  small. 

REFERENCES 

1.  Balfour,  D.  C,  "Splenectomy  for  Repeated  Gastro-intestinal  Hemor- 

rhages." Ann.  Surg.,  191 7,  LXV,  89-94. 

2.  Banti,  G.,  "Dell  anemia  splenica,"  Firenze,  1882,  70  p.  Repr.  from; 

"Pubb.  d.  r.  I  St  di  studi  sup.  ...  in  Firenze.  Sez.  di  med.  e.  chir." 

3.  Chabrol,   E.,  and  Benard,   H.,   "Present  Status  of  Splenectomy," 

Paris  mkd.t  1918,  VIII,  165.  Abstr.:  J.  Am.  M.  Ass.,  1918,  LXXI, 
1865. 

4.  Dock,  G.,  and  Warthin,  A.  S.,  "A  Clinical  and  Pathological  Study  of 

Two  Cases  of  Splenic  Anemia  with  Early  and  Late  Stages  of 
Cirrhosis."  Am.  J.  M.  5c.,  1904,  CXXVII,  24-55. 

5.  Fagge,  C.  H.,  "Principles  and  Practice  of  Medicine,"  Philadelphia, 

Blakiston,  1886,  II,  p.  304. 

6.  Giffin,  H.  Z.,  "Splenectomy  for  Splenic  Anemia  in  Childhood  and  for 

the  Splenic  Anemia  of  Infancy,"  Ann.  Surg.,  1915,  LXII,  679-687; 
"The  Treatment  by  Splenectomy  of  Splenomegaly  with  Anemia 
Associated  with  Syphilis,"  Am.  J.  M.  Sc,  1916,  CLII,  5-16. 

7.  Gretsel,  "Ein  Fall  von  Anaemia  splenica  bei  einem  Kinde,"  Berl. 

klin.  Wcbnscbr.,  1866,  III,  212-214. 

8.  Jonnesco,  T.,  "Splenectomie  pour  hypertrophic  palud^enne,"  Bull. 

et  mem.  Soc.  de  cbir.  de  Bucarest,  1899- 1900,  II,  3-7;  112;  190 1-2, 
IV,  58;  64;  also:  Internal.  Clin.,  1902,  IV,  221-231. 

9.  Osier,  W.,  "On  Splenic  Anemia,"  Am.  J.  M.  Sc,  1900,  CXIX,  54*73: 

"Diseases  of  the  Blood  and  Blood-glanduIar  System,"  in  Pepper, 
W.,  "System  of  Practical  Medicine,"  Philadelphia,  Lea,  1885,  III, 
882-950. 


SPLENIC  ANEMIA  looi 

10.  Moschowitz,  E.,  "A  Critique  of  Banti's  Disease,**  J.  Am.  M.  Ass., 

1917,  LXIX,  1045-1051. 

11.  Sherren,  J.,  "A  Note  on  the  Surgical  Treatment  of  Certain  Diseases 

by  Splenectomy,"  Ann.  Surg.,  1918,  LXVIII,  379-382. 

12.  Sippy,  B.  W.,  "A  Critical  Summary  of  the  Literature  on  Splenic 

Pseudoleuksemia  (Anaemia    Splenica;    Splenomegalie    Primitive),** 
Am.  J.  M.  Sc,  1899,  CXVIII,  570-586. 

13.  Warthin,  A.  S.,  "The  Relation  of  Thrombophlebitis  of  the  Portal  and 

Splenic  Veins  to  Splenic  Anemia  and  Banti's  Disease,**  Intemat. 
Clin.,  1910,  20  s.,  IV,  189-221. 

14.  Wood,  H.  C,  Jr.,  "On  the  Relations  of  Leucocythemia  and  Pseudo- 

leukemia," Am.  J.  M.  Sc,  1891,  LXII,  679-687. 


TUMOR  FORMATION  WITH  PEPTIC  ULCER 
By  Charles  G.  Stockton,  Buffalo,  N.  Y. 

CHRONIC  peptic  ulcer,  especially  near  the  pylorus,  whether 
occurring  in  stomach  or  duodenum,  often  gives  rise  to  tumor- 
like masses  that  arise  from  chronic  inflammation,  sometimes 
in  connection  with  the  process  of  slow  perforation. 

In  rare  instances  these  masses  are  carcinomatous;  in  others 
they  are  found  to  be  largely  inflammatory,  but  have  elements  of 
carcinoma  in  a  limited  area,  or  scattered  through  the  growth;  in  the 
majority  of  cases  they  show  no  characteristics  of  neoplasm,  and  are 
purely  inflammatory. 

The  gross  appearance  of  these  masses  is  much  alike,  whether 
carcinoma  or  inflammatory.  In  older  cases,  when  carcinomatous, 
there  may  be  expected  metastases,  direct  invasion  of  neighboring 
organs,  or  both. 

I  have  to  describe  a  case  which  demonstrates  that  even  without 
perforating,  a  chronic,  duodenal,  peptic  ulcer  may  cause  an  in- 
flammatory tumor  that  invades  neighboring  organs,  replacing  nor- 
mal tissue  in  Hver,  pancreas,  and  intestinal  wall,  assuming  the  apn 
pearance  in  all  respects  characteristic  of  carcinoma;  yet,  upon  micro- 
scopic study,  the  tumor  is  shown  to  be  a  fibrous  mass  of  scar-like 
tissue,  somewhat  suggestive  of  keloid. 

A  physician,  aged  sixty  years,  had  for  two  years  suffered  recurring 
attacks  of  epigastric  pain,  vomiting,  and  melena.  In  the  intervals  between 
attacks  he  had  practiced  his  profession  and  taken  solid  food.  On  October 
I,  19 1 6,  he  entered  the  Buffalo  General  Hospital  nearly  exsanguinated, 
with  marked  gastrectasis  from  pyloric  stenosis  and  spasm.  One  thousand 
c.c.  of  highly  acid  gastric  juice  was  aspirated  at  one  time.  The  case  corre- 
sponded to  those  formerly  classed  as  gastro-succorrhea  from  obstruction, 
and  was  characteristic  of  a  benign  process.  There  was  a  negative  Wasser- 
mann  reaction.  There  were  no  biliary  symptoms.  Under  the  effect  of  atropin 
a  duodenal  tube  entered  the  intestine  and  duodenal  feeding  was  employed 
with  the  hope  of  suflicient  restoration  to  admit  of  surgical  relief.  Three 

1002 


i- ,.;.  .-^rsiv:''^.-^. :' 


•«'»  «. 


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Fig.  1.     i;,VAo;u;-.  ui    uiu  Wall  oi   tiiil  Duodenum  vvitu  Nlw   1  o.x.iLD  iioixwio 
Tissue;  Atrophy  of  Muscle. 


Fig.  2.    New  Formed  Fibrous  Tissue  Extending  between  the  Lxjbules  of 
THE  Pancreas  and  Invading  the  Lobules. 


Fig.    3.    New    Formed    Fibrous  Tissue   Surrounding  the   Small    Bile    Ducts; 
Inflammatory  Cells  Invading  the  Lobules. 


TUMOR  FORMATION  WITH  PEPTIC  ULCER      1003 

hundred  c.c.  of  blood  was  transfused.  Marked  improvement  was  seen  for 
forty-eight  hours,  then  the  patient  became  delirious,  dragged  out  the 
tube,  went  into  collapse,  and  died  of  exhaustion,  without  further  hem- 
orrhage. 

Autopsy.  An  irregular,  nodular  tumor  was  found  invading  the  pylorus, 
the  first  portion  of  the  duodenum,  the  head  of  the  pancreas,  the  common 
bile  duct  (at  its  beginning  and  outlet),  the  duct  of  Wirsung,  the  gall 
bladder,  and  the  contiguous  portion  of  the  liver.  The  cut  surface  was  hard 
and  cartilaginous.  Posteriorly,  near  the  pyloric  ring,  there  was  a  deep, 
indurated,  peptic  ulcer  largely  occupied  by  a  thrombus,  about  which  was 
some  bleeding.  Although  there  were  no  metastases,  the  general  appearance 
was  that  of  carcinoma. 

The  microscopic  examination  by  Dr.  Herbert  U.  Williams  revealed  that 
there  was  exuberant  connective  tissue  growth  apparently  replacing  the 
normal  tissue  in  pylorus,  duodenum  (Fig.  i),  pancreas  (Fig.  2),  and  liver 
(Fig.  3).  The  inflammatory  cells  not  only  invaded  the  muscle  walls  of 
stomach  and  duodenum,  but  the  lobules  of  the  pancreas  and  liver.  The 
fibrous  tissue  extended  along  the  bile  radicles  between  the  lobules  of  the 
liver,  also  the  lobules  of  the  pancreas.  Small  vessels  were  thrombosed.  There 
were  many  much  thickened  capillaries  showing  hyalin  degeneration.  No 
evidence  of  cancer  was  discoverable. 

The  case  was  extraordinary  in  its  general  resemblance  to  cancer 
and  in  that  the  inflammatory  tissue  invaded  the  neighboring 
organs,  replacing  the  normal  tissue,  thus  resembling  the  method 
of  neoplasm. 

It  is  an  interesting  speculation  as  to  what  role  the  enzymes 
may  play  in  the  invading  tendencies  of  inflammatory  tumors  of 
this  kind. 


ANEURYSM  OF  THE  MIDDLE  CEREBRAL  ARTERY 
IN  A  CHILD  NINE  AND  ONE-HALF  YEARS  OLD 

By  Fritz  B.  Talbot,  M.D.,  Boston,  Mass. 

THIS  child,  nine  years  and  eight  months,  was  under  observation  for 
six  years.  His  family  history  was  negative.  He  was  first  seen  De- 
cember 24, 1 908,  for  bronchitis  at  the  age  of  four  and  one-half  years, 
from  which  he  rapidly  recovered.  In  1910  he  had  measles  and  was  moder- 
ately sick.  In  the  spring  of  191 1  he  had  whooping  cough  and  whooped 
very  badly.  In  November,  191 2,  he  had  an  attack  of  asthma  and  was  sick 
in  bed  for  three  or  four  days.  In  March,  1913,  his  appendix  was  removed. 
Since  that  time  he  had  complained  of  tenderness  about  the  head.  When- 
ever the  father  ruffled  his  hair  he  said  it  caused  considerable  pain  and  made 
him  feel  sick,  so  that  he  had  to  go  and  lie  down.  These  symptoms,  however, 
were  not  severe  enough  to  cause  the  parents  to  call  in  a  physician.  While 
at  breakfast  on  February  26,  19 14,  he  had  slight  nausea.  He  was  taken 
out  in  the  air  and  said  he  felt  better  and  acted  perfectly  well  the  rest  of  the 
day.  At  2  a.m.  on  February  27th  he  woke  up,  was  nauseated  and  vomited 
and  complained  of  pain  in  his  head.  The  parents  gave  him  ipecac  and 
cleared  out  the  bowels.  Shortly  after  that  he  commenced  to  have  con- 
vulsions. He  was  seen  at  5  a.m.  on  February  27th  and  found  to  have  a 
Babinsky  and  Kernig  sign.  The  right  pupil  was  very  much  contracted  and 
pin-point  in  size.  The  left  pupil  was  dilated,  and  the  right  side  of  the  body 
was  paralyzed.  He  had  Cheyne-Stokes*  respiration.  His  physical  examina- 
tion was  otherwise  normal.  The  convulsions  became  worse,  and  respiration 
stopped  about  6  a.m.  After  he  had  artificial  respiration  for  a  few  minutes 
he  commenced  breathing  again.  A  lumbar  puncture  was  done  in  the  third 
inter-space  and  brought  forth  bloody  fluid,  which  came  drop  by  drop, 
without  any  pressure.  About  20  c.c.  was  removed  and  the  patient  im- 
proved. It  was  believed  that  the  blood  was  an  accidental  result  of  the 
lumbar  puncture,  and  that  the  disease  might  be  cerebro-spinal  meningitis; 
2  c.c.  of  anti-meningitis  serum  was,  therefore,  injected  very  slowly.  This 
was  discontinued,  however,  because  the  respirations  again  stopped,  and 
artificial  respiration  was  necessary.  The  needle  was  soon  reintroduced  into 
the  spinal  canal  and  more  bright  red  blood  obtained.  This  time  there  was 
no  improvement  in  the  symptoms.  The  patient  died  an  hour  later.  The 
temperature  twice  taken  by  rectum  was  found  to  be  normal. 

1004 


ANEURYSM  OF  MIDDLE  CEREBRAL  ARTERY     1005 

PosT-MoRTEM  Examination.  The  p>ost-mortem  examination  was  per- 
formed by  Dr.  Howard  T.  Karsner  nine  and  a  half  hours  later. 

Body.  Autopsy  showed  a  body  of  a  well-nourished,  well-grown  white 
boy  with  extreme  rigor  mortis.  Incisions  were  limited  to  the  head  and  back. 
Incision  through  scalp  showed  nothing  unusual.  The  saw-cut  through  the 
skull  released  a  great  deal  of  fluid  blood  under  pressure,  and  the  entire 
vertex  of  the  brain  was  found  to  be  covered  with  blood,  more  particularly 
on  the  left  side. 

Brain.  The  pia  appeared  to  show  a  very  slight  degree  of  roughening 
and  was  covered  with  blood.  The  vessels  were  much  dilated  and  the  sulci 
filled  with  blood.  The  base  of  the  brain  showed  normal  arteries,  an  enor- 
mous amount  of  blood  under  the  pia  and  in  the  arachnoid,  extending  from 
a  slight  distance  in  front  of  the  optic  commissure  to  the  medulla  and 
laterally  well  up  into  the  sylvian  fissures.  A  single  incision  vertically  through 
the  brain  showed  a  large  amount  of  blood  in  the  left  ventricle. 

The  brain  was  suspended  in  formalin  overnight  and  several  more 
sections  made  on  the  morning  of  February  28th.  These  sections  showed  in 
the  left  hippocampus  a  cyst  whose  walls  measured  1.5  mm.  in  thickness 
and  about  2  cm.  in  diameter.  The  cyst  was  filled  with  fresh  blood  clot 
(proven  fresh  by  histological  section),  and  around  the  outer  wall  of  the 
cyst  was  a  large  amount  of  fresh  clot  reaching  to  a  depth  of  from  3  to  4 
mm.  As  far  as  could  be  seen  from  the  section,  the  hemorrhages  appeared 
to  have  extended  from  this  region  up  into  the  anterior  cornu  of  the  left 
ventricle. 

Cord.  The  cord,  upon  removal,  showed  a  considerable  amount  of  fluid, 
under  the  pia  and  in  the  arachnoid,  throughout  its  entire  length.  Trans- 
verse section  showed  a  slight  pink  tinge  about  the  gray  matter.  Histological 
section,  on  the  morning  of  February  28th  (frozen  section),  failed  to  show 
any  sign  of  poliomyelitis. 

Further  examination  of  the  fully  hardened  brain  showed  the  cyst  to 
be  an  aneurysm  of  the  beginning  of  the  middle  cerebral  artery.  In  the  base 
of  the  brain  this  vessel  could  be  seen,  and  upon  dissection  it  was  found  to 
enlarge  and  form  the  aneurysmal  sac.  The  anterior  choroid  artery  could 
not  be  positively  identified.  Above  and  in  the  lateral  aspect  of  the  sac  was 
found  the  continuation  of  the  middle  cerebral  artery,  and  as  it  continued 
its  course  from  the  sac  it  almost  immediately  gave  off"  the  p>erforating 
branches  and  then  the  usual  branches.  The  sac  was  irregular  in  its  inner 
wall,  but  all  the  clot  appeared  to  be  fresh  clot  and  there  was  no  evidence 
of  the  brain  substance  having  suff'ered  from  lack  of  nutrition.  The  clot 
around  the  sac  was  of  varying  depth,  from  2  to  5  mm.,  and  was  fairly 
sharply  defined  from  the  brain  tissue.  The  whole  mass  pushed  upward 


ioo6    ANEURYSM  OF  MIDDLE  CEREBRAL  ARTERY 

and  outward  the  tissues  of  the  anterior  perforated  space,  and  the  temporo- 
sphenoidal  lobe  and  the  optic  nerves  and  commissure  appeared  to  be  free 
from  pressure.  The  coronal  section  of  the  optic  thalamus  showed  a  few 
large  punctae  hemorrhagicse,  but  no  definite  hemorrhage,  and  the  remains 
of  the  brain  substance  failed  to  show  hemorrhage. 

The  left  lateral  ventricle  was  filled  and  distended  with  blood,  which 
also  was  found  in  the  third  and  fourth  ventricles.  A  perfect  cast  of  the 
fourth  ventricle  was  formed  by  the  hardened  clot.  The  clot  showed  that  the 
blood  extended  into  the  foramen  of  Magendie.  There  was  also  a  very  small 
amount  of  blood  in  the  right  lateral  ventricle. 

No  definite  point  of  rupture  of  the  sac  could  be  made  out,  but  it  seemed 
most  probable  that  the  rupture  was  upward  and  into  the  anterior  cornu 
of  the  lateral  ventricle,  and  thence  to  the  outer  surface  of  the  brain  by  way 
of  the  foramen  of  Magendie.  A  small  area  was  found,  however,  in  the  in- 
ferior surface  of  the  aneurysm  which  may  have  served  as  a  point  of  origin 
of  the  external  hemorrhage.  This  was  sent  through  for  histological  exami- 
nation. 

Microscopical  sections  from  various  parts  of  the  walls  of  the  aneurysm  *' 
were  stained  with  hematoxylin  and  eosin  phosphotungstic  acid,  hematoxy- 
lin and  eosin,  and  by  the  elastica  method.  Additional  sections  from  other 
parts  of  the  brain  were  stained  with  hematoxylin  and  eosin. 

The  study  of  these  sections  showed  the  aneurysm  wall  to  be  made  up 
largely  of  connective  tissue,  externally  old  and  dense,  internally  younger, 
accompanied  by  new  blood  vessels  and  apparently  of  a  sort  of  granulation 
tissue.  At  the  point  of  origin  of  the  aneurysm  from  the  vessel,  the  elastica 
extended  a  short  distance  into  the  aneurysm  wall,  but  was  soon  lost,  and 
more  remote  parts  of  the  aneurysms  showed  only  a  few  fragments  of  curled 
elastic  fibrils.  Near  the  internal  surface  of  the  aneurysmal  wall  were  found 
a  few  strands  of  fibrin  enmeshed  in  the  granulation  tissue  spoken  of  above. 
The  muscular  tissue  of  the  artery  extended  into  the  aneurysm  wall  for 
about  the  same  distance  as  the  elastica,  namely,  about  3  mm.,  and  was 
then  lost. 

A  section  of  aneurysm  wall  was  stained  by  the  Levaditi  method  and 
examined  thoroughly  with  oil  immersion  lens  and  mechanical  stage  and 
no  treponemata  found.  Included  in  the  sections  were  numerous  large 
branches  of  the  basal  vessels  of  the  brain,  two  of  these  showing  well- 
marked  thickening  of  the  intima  in  focal  areas.  The  perivascular  lymphatics 
in  places  near  the  hemorrhage  frequently  contained  blood,  but  there  were 
no  miliary  aneurysms  nor  evidence  of  hemorrhage  elsewhere  into  brain 
tissue.  The  section  of  supposed  point  of  rupture  of  aneurysm  showed 
nothing  that  could  be  safely  interpreted  as  a  point  of  rupture,  although  the 


ANEURYSM  OF  MIDDLE  CEREBRAL  ARTERY     1007 

wall  was  very  much  thinned.  Sections  of  spinal  cord  showed  nothing 
abnormal. 

The  Wassermann  reaction  of  the  spinal  fluid  was  slightly  positive,  but 
since  the  fluid  was  proven  to  be  richly  contaminated  with  Bacillus  coli 
communi,  the  reaction  must  be  considered  of  little  value. 

Summary.  The  case  is  regarded  pathologically  as  an  aneurysm  following 
the  vascular  lesion  of  some  acute  infection.  The  sclerosis  in  this  case  is 
purely  intimal  in  type  and  not  the  medial  sclerosis  of  syphilis.  As  further 
arguments  against  syphilis  are  to  be  considered  the  practically  negative 
Wassermann  and  the  finding  of  no  organisms  by  the  Levaditi  method;  in 
addition  must  also  be  considered  the  absolutely  negative  history.  On  the 
basis  of  probability,  vascular  lesions  in  childhood  are  much  more  fre- 
quently the  result  of  acute  infections  than  of  syphilis.  If  syphilis  were 
present  in  the  case  it  is  hardly  likely  that  it  would  have  attacked  only 
the  arteries  and  left  the  patient  well  in  other  respects. 

The  rupture  of  the  aneurysm  may  have  been  determined  by  the  active 
exercise  of  the  day  with  its  concordant  high  blood  pressure.  The  point  of 
rupture  could  not  be  made  out  with  certainty.  Whether  the  rupture  was 
through  the  inferior  surface  of  the  aneurysm  or  not,  it  seems  certain  that 
most  of  the  blood  passed  into  the  left  ventricle,  and  because  of  this  fact  it 
is  presumed  that  the  rupture  was  through  the  superomesial  surface,  into 
the  left  anterior  horn,  the  left  ventricle,  the  third  and  fourth  ventricle, 
and  thence  into  the  pia  arachnoid  space. 

Discussion.  The  diagnosis  of  aneurysm  of  the  cerebral  artery  was,  of 
course,  not  made  during  life,  nor  was  it  even  suspected.  When  the  lumbar 
puncture  was  performed  the  presence  of  bloody  fluid  gave  a  puzzling  pic- 
ture, as  it  was  supposed  that  we  were  dealing  either  with  a  case  of  cerebro- 
spinal meningitis,  or  infantile  paralysis.  The  lumbar  puncture  very  fre- 
quently results  in  blood-tinged  fluid.  The  fact  that  the  fluid  continued 
to  run  bloody,  however,  and  did  not  clear  up  at  all,  might  be  used  as  an 
argument  against  it  being  accidental,  and  that  the  blood  had  a  causative 
connection  with  the  illness.  The  cause,  however,  was  not  revealed  until 
post-mortem  examination. 

The  etiology  of  aneurysm  of  the  cerebral  artery  shows  that  males 
are  more  frequently  affected  than  females.  Although  the  disease  is 
most  common  in  middle  life,  it  is  rarely  ever  found  among  infants 
and  children.  Osier  reports  a  case  in  a  lad  of  six,  and  other  writers 
report  aneurysm  even  in  infants.  Leboeuf  (i)  reported  twenty-four 
cases  of  aneurysm  in  infancy  which  he  had  gathered  from  litera- 
ture and  were  mostly  aneurysm  of  the  aorta.   Phanomenow  (2) 


ioo8    ANEURYSM  OF  MIDDLE  CEREBRAL  ARTERY 

rep)orted  aneurysm  of  the  abdominal  aorta  found  while  dissecting  a 
fetus.  Another  case  of  aneurysm  of  the  aorta  was  also  reported  by 
Durante  (3)  discovered  in  the  same  manner.  It  is  believed  by  the 
French  writers  that  there  are  two  congenital  aneurysms. 

John  Collins  Warren  (4)  says  that  intra-cranial  aneurysm  is  per- 
haps the  most  common  variety  of  spontaneous  aneurysm  in  children. 
He  quotes  Church,  who  published  a  table  of  thirteen  cases  in  sub- 
jects under  twenty  years  of  age.  In  seven  of  these  cases  heart  dis- 
ease existed,  and  in  six  of  these  there  were  vegetations  upon  the 
valves.  He  regards  this  form  of  aneurysm  as  due  to  emboHsm  and 
is  inclined  to  think  that  disease  of  the  arterial  wall  is  rarely  if  ever 
a  cause  of  the  disease.  West  (5)  reports  a  case  of  aneurysm  of  the 
left  middle  cerebral  artery  in  a  boy  twelve  years  old  following 
scarlet  fever  at  eight  years  of  age. 

Speaking  of  aneurysm  in  general,  Hochsinger  (6)  says  that 
according  to  Liddell,  who  has  grouped  243  special  cases  of  aneurysm 
according  to  age,  7  occurred  in  children  from  two  to  five  years  of 
age;  i  from  five  to  ten  years,  and  2  from  ten  to  fifteen  years;  in  all 
ID  during  childhood.  The  disease,  therefore,  is  rare  in  childhood. 

The  etiology  in  the  case  of  this  patient  is  not  clear.  Congenital 
syphilis  can  be  practically  excluded  by  the  absence  of  a  family 
history  of  miscarriages  and  infection  of  either  parent,  and  by  the 
lack  of  a  strongly  positive  Wassermann.  Thrombosis  is  ruled  out 
by  the  p>ost-mortem  examination.  The  previous  history  of  measles, 
whooping  cough,  and  an  infected  appendix  requiring  operation, 
give  the  only  clue  to  a  possible  source  of  infection  of  the  arterial 
wall.  None  of  these  three  diseases  alone  would  seem  enough  to  be 
the  whole  cause.  It  is  possible,  on  the  other  hand,  that  the  violent 
paroxysms  of  coughing  during  the  pertussis  may  have  weakened 
the  arterial  wall  of  the  cerebral  artery  and  made  it  more  susceptible 
to  infection.  The  suffusion  of  the  face  during  severe  paroxysms  of 
coughing  in  pertussis  and  the  frequently  small  hemorrhages  inside 
the  skull  lend  strength  to  this  assumption. 

The  symptoms  outlined  are  very  obscure.  It  is  possible  that  if 
the  child  had  been  examined  during  life  with  aneurysm  in  view,  that 
it  might  have  been  diagnosed,  but  the  slight  symptoms  of  feeling 
bad  because  of  his  hair  being  ruffled  did  not  lead  the  parents  to 
consult  a  physician. 


ANEURYSM  OF  MIDDLE  CEREBRAL  ARTERY     1009 

The  treatment  was,  of  course,  absolutely  hopeless,  and  one  might 
wonder  if  the  disease  had  been  recognized  ante-mortem  whether 
any  treatment  could  have  resulted  in  repair, 

BIBLIOGRAPHY 

1.  Leboeuf,  Th^se  de  Bordeaux,  1898. 

2.  Ph'anomenow,  Arcb.J.  Gynaekoi,  1881,  XVII,  133. 

3.  Durante,  Soc.  anat.,  1899. 

4.  Warren,  John  Collins,  Keating,  II,  868. 

5.  West,  Path.  Trans.,  1881,  XXXII. 

6.  Hochsinger,   Pfaundler  and  Schlossmann,   "Diseases   of  Children," 

III,  521. 


OBSERVATIONS  ON  CONGENITAL  HYPERTROPHY 
OF  THE  PYLORUS 

By  John  Thomson,  M.D. 

Consulting  Physician  to  the  Royal  Hospital  for  Sick  Children,  Edinburgh 

THE  clinical  material  on  which  the  following  remarks  are 
founded  consists  in  lOO  consecutive  cases  of  congenital  pyloric 
hypertrophy  which  have  been  treated  in  hospital  and  private 
practice  during  the  last  twenty-five  years  (February,  1894,  to  Feb- 
ruary, 1 919).  A  table  of  these  is  appended,  and  care  has  been  taken 
to  include  in  it  only  those  cases  in  which  the  diagnosis  seemed  be- 
yond a  doubt.  Of  the  58  cases  which  ended  fatally,  45  were  examined 
post-mortem;  and,  of  the  remaining  13  in  which  this  was  not  al- 
lowed, the  condition  of  the  pylorus  had  been  ascertained  during  an 
operation  in  4  instances. 

The  aim  of  the  paper  is  to  sum  up  briefly  the  writer's  personal 
experience  of  a  large  number  of  cases,  many  of  which  were  studied 
for  an  unusually  long  time.  The  subjects  specially  dealt  with 
comprise  the  family  history  and  complications,  the  causation  of 
the  muscular  hypertrophy  and  of  the  symptoms,  the  natural  course 
of  the  disease  under  medical  and  surgical  treatment,  the  symptoms 
and  choice  of  treatment  in  different  types  of  the  disease,  the  diag- 
nosis, especially  that  between  pyloric  hypertrophy  and  the  so-called 
"pyloric  spasm,"  the  diflPerence  in  the  prognosis  in  hospital  and 
private  cases,  and  the  subsequent  health  of  the  patients  who 
recover. 

Family  Occurrence.  In  one  of  the  cases  (No.  11)  the  father  had  suf- 
fered as  a  baby  from  similar  symptoms.  In  another  (No.  83)  the  mother's 
brother  had  died  in  infancy  from  what  certainly  seems  to  have  been 
congenital  pyloric  hypertrophy.  The  father  and  paternal  uncle  of  No.  13, 
who  were  Jews,  had  practised  rumination  since  childhood. 

In  four  instances  there  were  two  members  of  a  family  affected,  namely 
Nos.  14  and  34;  24  and  29;  33  and  36;  and  38  and  54.  One  of  the  patients 
(No.  86)  was  a  twin,  the  other  twin  being  normal. 

lOIO 


CONGENITAL  HYPERTROPHY  OF  PYLORUS   loii 

Complications.  In  No.  36  there  was  a  congenital  heart-lesion.  One 
patient  (No.  46)  whom  I  saw  in  consultation  with  Dr.  D.  B.  Lees,  was 
the  subject  of  achondroplasia  and  died  about  a  year  later  from  hydro- 
cephalus— long  after  the  stomach  symptoms  had  ceased.  With  these  ex- 
ceptions, no  accompanying  congenital  malformations  or  diseases  were 
observed. 

One  child  (No.  96)  was  found  on  admission  to  hospital  to  be  suffering 
from  acute  haemorrhagic  nephritis  which  was  rapidly  fatal.  Another 
(No.  27)  died  from  broncho-pneumonia  ten  days  after  admission  to  hos- 
pital. 

The  complication  most  to  be  feared  is  acute  infective  diarrhoea. 
When  this  occurs,  as  it  is  apt  to  do  in  a  hospital  ward  during  summer  or 
autumn,  the  risk  is  very  great;  for  children  with  pyloric  hypertrophy 
seem  to  be  peculiarly  liable  to  suffer  seriously  from  this  form  of  infection. 
Three  of  the  hospital  cases  (Nos.  54,  $6,  and  62)  died  from  it  while  they 
were  improving  rapidly  under  medical  treatment;  one  (No.  60),  also 
treated  medically,  died  two  months  after  all  his  pyloric  symptoms  had 
ceased;  and  a  third  (No.  20)  a  month  after  a  successful  gastro-enterostomy. 

In  one  case  (No.  47)  the  patient,  who  ultimately  did  well,  suffered 
for  about  three  years  after  gastro-enterostomy  from  recurrent  attacks  of 
vomiting. 

Causation  oj  the  Miiscular  Hypertrophy  and  of  the  Symptoms. 
The  extended  clinical  and  pathological  experience  which  these 
cases  have  afforded  has  served  to  confirm  former  conclusions  re- 
garding its  primarily  nervous  origin,  although  this  does  not  seem  to 
be  the  only  cause  of  the  obstruction. 

When  we  examine  the  essential  structural  change  that  is  present, 
we  find  that  it  is  definitely  restricted  to  the  upper  part  of  the 
ahmentary  tract  and  consists  simply  in  a  high  degree  of  true 
hypertrophy  of  the  entire  muscular  coat  of  the  pylorus  and  adjacent 
stomach- wall,  and  a  lesser  amount  of  the  same  in  the  cardiac  end 
of  the  stomach  and  in  the  oesophagus.  The  other  local  changes 
present,  such  as  dilatation  of  the  stomach  and  oesophagus,  gastric 
catarrh,  and  general  wasting  of  the  body,  are  obviously  secondary 
results  of  the  pyloric  obstruction. 

The  essential  abnormality  of  Junction  may  be  said  to  be 
similarly  localised.  It  consists  mainly  in  an  ill-timed  abnormally 
forcible  and  prolonged  contraction  of  the  pyloric  muscle,  which 
prevents  the  food  passing  into  the  bowel,  and  so  accounts  for  the 


I0I2  CONGENITAL  HYPERTROPHY  OF  PYLORUS 

starvation  and  wasting,  the  thirst  and  drying-up  of  the  tissues, 
and  the  scantiness  of  the  urine  and  fseces.  In  conjunction  with  the 
muscular  hypertrophy  of  the  stomach-wall  it  also  explains  the 
forcible  vomiting. 

While  these  facts  can  scarcely  be  disputed,  there  is  still  some 
difference  of  opinion  regarding  the  origin  of  the  muscular  hyper- 
trophy. Is  the  abnormal  action  of  the  pylorus  and  other  parts  a 
secondary  phenomenon,  due  to  the  muscular  coat  being  primarily 
affected  by  a  simple  congenital  redundancy  of  growth,  as  Hirsch- 
sprung, Cautley,  and  others  have  suggested?  Or,  is  the  functional 
abnormality  to  be  regarded  as  the  primary  element  in  the  process — 
the  muscle  being  hypertrophied  merely  because,  from  an  early 
period  of  its  development,  it  has  been  worried  into  overgrowth  by 
constantly  recurring  overaction,  such  as  would  result  from  even  a 
slight  degree  of  habitual  inco-ordination? 

As  these  two  hypotheses  have  been  fully  dealt  with  in  a  former 
paper  (i)  they  need  not  be  further  discussed  here.  I  may,  however, 
give  a  brief  statement  of  the  second  of  them,  which  seems  to  me 
altogether  the  more  likely  of  the  two. 

It  is  known  that  the  normal  foetus  swallows  a  considerable  quan- 
tity of  amniotic  fluid  during  intra-uterine  life;  and,  as  this  implies 
a  certain  amount  of  co-ordinated  muscular  action  of  the  stomach 
and  pylorus,  it  is  believed  that  the  supposed  inco-ordination  between 
these  parts  begins  when  the  fluid  first  passes  through  them.  There 
is  reason  to  believe,  however,  that  the  muscular  action  may  not  at 
this  period  be  very  vigorous  or  continuous,  and  that  therefore,  by 
the  time  the  child  is  born,  only  a  small  degree  of  hypertrophy  will 
have  occurred.  After  birth,  when  regular  feeding  has  begun,  the 
force  of  the  muscular  action  and  the  inco-ordination  will  tend  to 
increase  so  that  the  hypertrophy  will  progress  much  more  rapidly 
than  during  intra-uterine  life.  It  is  in  accordance  with  medical, 
surgical,  and  pathological  experience  that  the  pyloric  tumour  does 
grow  larger  and  harder  while  the  active  symptoms  continue.  This 
is  just  what  might  be  expected,  for,  as  John  Hunter  pointed  out 
long  ago,  a  tendency  to  hypertrophy  as  the  result  of  repeated  forcible 
contractions  is  "a  property  of  all  muscles"  and  is  greater  in  in- 
voluntary than  in  voluntary  muscles.  It  is  also  extremely  probable 
that  tissue-growth  of  this  sort  is  specially  active  in  early  infancy. 


Fig.  I. 


Fig.  2. 


Fig.  1.    Transverse  Section  of  Normal  Pylorus  near  the  Duodenum,  X  4 
DiAM.  Child  of  Nine  Weeks. 

Fig.  2.    Transverse  Section  of  Hypertrophied  Pylorus  near  the  Duodenum, 
X  4  Diam.  Child  of  Nine  Weeks. 

Photographs  by  Mr.  Richard  Muir. 


CONGENITAL  HYPERTROPHY  OF  PYLORUS  1013 

In  the  blocking  of  the  pylorus  there  are  two  factors  at  work. 
There  is  first  the  abnormal  muscular  contraction,  and,  secondly, 
the  mechanical  effect  of  the  increased  bulk  of  the  muscular  tissue. 
This  second  factor  is  worthy  of  more  attention  than  it  has  hitherto 
received. 

When  one  contrasts  a  transverse  section  of  a  normal  pylorus 
with  one  from  a  case  of  pyloric  hypertrophy  (Figs,  i  and  2),  the 
degree  to  which  the  mere  bulk  of  the  hypertrophied  muscle  must 
diminish  the  pyloric  lumen  is  obvious. 

The  muscular  coat,  as  we  have  seen,  grows  quickly;  but  the 
peritoneal  tube  enlarges  comparatively  slowly  with  the  general 
growth  of  the  body,  and  is  incapable  of  more  than  a  moderate  dis- 
tension. The  rapidly  thickening  muscle,  therefore,  presses  more  and 
more  inwards  as  it  grows,  and  the  tube  of  mucous  membrane  is 
elongated  and  increasingly  narrowed.  The  stage  at  which  the 
symptoms  become  typical  in  any  case  probably  depends  mainly  on 
when  the  muscular  layer  has  become  so  thick  that,  even  during 
relaxation,  it  seriously  embarrasses  the  functional  opening  of 
the  canal  for  the  passage  of  food.  As  the  rate  of  increase  of  the 
muscular  hypertrophy  varies  in  different  children,  there  is  a  corre- 
sponding difference  in  the  age  at  which  severe  obstructive  symp)- 
toms  occur.  This  is  the  apparent  explanation  why  the  violent 
vomiting  sets  in  as  early  as  the  seventh  or  eighth  day  of  life  in 
some  cases,  while  in  others  it  does  not  occur  until  the  sixth  or 
eighth  week. 

The  Natural  Course  of  Recovery  from  the  Disease.  In  considering 
the  question  of  the  treatment  of  pyloric  hypertrophy,  we  have 
to  bear  in  mind  an  important  fact  regarding  its  natural  history 
which  has  been  strongly  emphasized  by  Robert  Hutchison — that 
the  disease  is  self-limited,  in  the  sense  that  the  pyloric  lumen  will 
eventually  open  up  spontaneously  and  the  child  recover  completely, 
provided  he  does  not  die  in  the  process.  When  such  spontaneous 
recovery  occurs,  we  know  from  post-mortem  experience  that  the 
muscular  coat  remains  thickened  for  a  long  time,  although  its 
action  has  become  gradually  normal.  Probably  the  muscular  hyper- 
trophy slowly  lessens  when  the  tendency  to  spasm  has  ceased,  and 
doubtless  the  peritoneal  tube  goes  on  steadily  widening  also  in 
the  course  of  growth,  so  that  the  lumen  of  the  pylorus  becomes  less 


I0I4     CONGENITAL  HYPERTROPHY  OF  PYLORUS 

and  less  compressed;  ultimately,  the  channel  having  become  large 
enough  for  practical  purposes,  the  passage  of  food  takes  place 
normally. 

This  natural  opening-up  of  the  lumen  is  usually  a  protracted, 
and  often  rather  a  risky  process.  Its  progress  is  best  estimated 
by  watching  the  child's  weight,  which  should  if  possible  be  taken 
daily  throughout  the  illness.  How  it  usually  proceeds  is  seen  in  the 
accompanying  series  of  weekly  charts.  These  show  the  obstinate 
manner  in  which  the  weight  often  refuses  to  go  up  for  many  weeks 
after  the  medical  treatment  has  begun,  and  the  steadiness  and 
rapidity  with  which  it  rises  once  the  pyloric  lumen  has  begun  to 
widen.  Evidently  what  we  may  expect  from  medical  treatment  in 
most  cases,  is  not  so  much  that  we  can  greatly  hasten  the  opening 
of  the  passage  by  what  we  do,  as  that  we  may  be  able  to  relieve 
it  just  sufl5ciently  to  keep  the  child  alive,  in  spite  of  the  continuance 
of  the  obstruction,  until  the  natural  process  of  recovery  has  had 
time  to  occur. 

If  the  pyloric  lumen  is  efficiently  opened  up  by  a  surgical  opera- 
tion, however,  the  gain  in  weight  usually  sets  in  rapidly,  as  is  seen 
in  the  weight-charts  of  Nos.  8,  8i  and  90.  Occasionally,  as  in 
No.  67,  the  channel  has  not  been  opened  sufficiently  by  the 
operation,  and  symptoms  of  recovery  do  not  begin  till  many  weeks 
later. 

The  Symptoms  and  Treatment  of  the  Different  Types  of  the  Disease. 
The  choice  of  treatment  in  cases  of  congenital  pyloric  hyper- 
trophy must  depend  to  a  large  extent  on  the  degree  of  severity  of 
the  case.  This  is  ascertained  partly  from  the  history  of  the  symp- 
toms and  the  present  condition  of  the  child,  but  chiefly  by  investi- 
gating, in  a  preliminary  way,  the  eff^ect  that  regulation  of  the  diet 
and  stomach-washing  have  on  the  vomiting  and  on  the  gain  in 
weight.  According  to  the  result  of  these  measures  we  may  class 
the  cases  as  ordinary,  acute,  and  mild. 

In  the  majority  of  cases  of  the  ordinary  type  there  is  no  vomiting 
at  all  during  the  first  week  or  two  of  life,  and  the  child  gains  in 
weight  and  vigour  quite  normally.  In  some,  however,  we  are  told 
that  there  has  been,  even  from  birth,  an  occasional  "putting  up'* 
of  a  mild  character — the  milk  being  gently  returned  after  the  breast 
or  bottle  has  been  taken.  Often  the  typical  copious  "shooting" 


CONGENITAL  HYPERTROPHY  OF  PYLORUS   1015 

vomiting  sets  in  quite  suddenly  without  any  apparent  cause. 
The  date  of  its  onset  varies,  but  it  is  very  rare  for  it  to  begin  during 
the  first  week,  if  indeed  this  ever  occurs.  It  commonly  starts  between 
the  second  and  fourth,  and  sometimes  only  appears  as  late  as  the 
sixth  or  eighth  week.  In  five  of  my  cases  (Nos.  17,  39,  66y  83, and 
87)  the  vomiting  was  never  forcible.  Once  the  violent  vomiting 
begins,  it  usually  continues  at  short  intervals  until  special  treat- 
ment is  begun  to  stop  it.  The  rapid  loss  of  weight  and  the  other 
signs  of  want  of  fluid  absorption  may  set  in,  either  before  or  after 
the  characteristic  vomiting. 

When  the  usual  symptoms  are  recognised,  the  preliminary 
treatment  must  begin  at  once.  The  size  of  the  feeds  should  be 
restricted  to  2  oz.  or  less,  and  the  proportion  of  curd  and  fat  in 
them  lessened;  and  they  should  be  given  at  regular  intervals  of  two 
or  three  hours.  At  the  same  time,  the  stomach  should  be  washed 
out  with  warm  water  once  or  twice  a  day.  In  this  type  of  case  such 
treatment  almost  always  produces  an  immediate  effect.  The  vomit- 
ing ceases,  the  child  is  much  more  comfortable,  and  he  often  begins 
to  gain  a  little  weight;  although  in  most  cases  the  symptoms  recur 
whenever  an  attempt  is  made  to  increase  the  food  given  to  anything 
like  a  normal  amount. 

Further  treatment  by  hot  fomentations  over  the  stomach,  and 
the  administration  of  sedatives  such  as  opium  or  belladonna,  I 
have  never  found  of  much  value. 

A  considerable  proportion  of  hospital  cases,  and  also  some 
private  ones  are  only  brought  for  treatment  after  they  have  under- 
gone a  long  course  of  unsuitable  feeding,  and  the  child  is  in  a  state 
of  collapse,  and  has  dilatation  and  catarrh  of  the  stomach.  Under 
these  circumstances  the  most  urgent  indication  is  to  stop  all  food 
for  at  least  twenty-four  hours,  and  to  give  subcutaneous  injections 
of  normal  saline  solution  every  four  to  six  hours.  The  effect  of  these 
on  the  child's  strength  and  comfort  is  very  striking.  Most  infants 
bear  them  well,  but  there  are  a  few  whose  subcutaneous  tissues  are 
so  sensitive  that  the  injections  cause  them  considerable  pain. 
Nutrient  enemata  are  of  no  use,  but  it  is  always  well  if  possible  to 
supplement  the  subcutaneous  injections  by  enemata  of  normal 
saline  solution  (one  or  two  ounces  every  six  hours).  Some  children 
are  able  for  days  to  retain  these  without  difficulty,  but  many  resent 


ioi6      CONGENITAL  HYPERTROPHY  OF  PYLORUS 


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CONGENITAL  HYPERTROPHY  OF  PYLORUS      1017 

them  more  than  they  do  the  subcutaneous  infusions,  so  that  they 
have  to  be  given  up. 

If,  after  two  or  three  weeks,  the  child  is  failing  to  respond  to 
medical  treatment,  or  sooner  if  he  is  rapidly  losing  strength,  a  surgical 
operation  should  be  advised;  and  recent  experience  has  shown  that 
Rammstedt's  operation  is  preferable  in  every  respect  to  any  other 
form  of  surgical  procedure.  It  is  very  important  that  after  the 
operation,  and  until  recovery  has  set  in,  the  case  should  continue  to 
have  the  closest  attention  of  both  the  physician  and  the  surgeon. 

In  the  acute  cases  the  vomiting  usually  begins  very  early,  and  it 
sometimes  becomes  rapidly  so  urgent  that  not  even  a  teaspoonful 
of  water  can  be  retained. 

The  first  case  of  the  disease  I  ever  saw  was  a  typical  instance  of 
this  variety.  (2)  The  patient  (No.  i)  throve  fairly  well  on  the  bottle 
for  the  first  ten  days  of  life.  Forcible  vomiting  set  in  suddenly  on  the 
eleventh  day  and  persisted  continuously,  in  spite  of  careful  dieting 
and  lavage,  till  the  child  died  of  inanition  when  he  was  twenty- 
eight  days  old. 

This  acute  type  is  not  often  met  with.  Among  the  earlier  reported 
cases,  indeed,  it  figured  to  a  fairly  large  extent,  but  that  was  be- 
cause, at  the  time,  the  cases  with  milder  symptoms  were  usually 
not  recognised  as  instances  of  this  disease.  The  fact  that  few  except 
the  worst  cases  were  then  diagnosed,  accounts  for  the  formerly 
expressed  opinions  that  the  disease  is  very  rare  indeed  and  that  it 
never  recovers  without  operation. 

Whenever  a  case  of  pyloric  hypertrophy  proves  by  its  failure  to 
respond  at  all  to  preliminary  treatment,  to  be  of  this  type,  it  is  ad- 
visable to  have  it  operated  on  without  delaying  longer  than  is 
necessary  to  confirm  the  diagnosis;  and  it  may  occasionally  be 
desirable,  in  typical  cases,  to  call  in  the  surgeon  even  before  the 
characteristic  visible  peristalsis  has  begun,  as  was  done  in  Nos. 
34,  43,  and  47.  By  doing  so,  we  prevent  the  otherwise  probable 
dilatation  and  catarrh  of  the  stomach,  and  avoid  further  weakening 
of  the  patient  before  the  operation.  The  degree  of  muscular  hyper- 
trophy is  always,  I  think,  considerable  in  these  acute  cases. 

The  very  mild  cases  show  an  entirely  different  clinical  picture. 
They  are  not  at  all  uncommon,  and  it  is  probable  that  many  of 
them  recover  with  careful  dieting  only,  and  without  a  correct 


ioi8  CONGENITAL  HYPERTROPHY  OF  PYLORUS 

diagnosis  having  ever  been  made.  It  is  also  probable  that,  if  they 
were  all  recognised  and  suitably  treated  in  the  early  stages,  there 
would  be  many  fewer  dangerous  examples  of  the  ordinary  type  to 
be  treated  later.  The  increasing  number  of  mild  cases  in  recent 
reports  must  be  remembered  when  we  compare  the  older  with  the 
more  recent  statistics  of  the  results  of  treatment.  The  mild  cases 
are  not  generally  seen  by  the  physician  until  they  are  two  or  three 
months  old,  or  later.  They  never  require  surgical  treatment.  The 
following  (No.  37)  is  one  of  the  most  typical  instances  of  this  variety 
I  have  seen. 

A  girl  of  eleven  weeks,  who  had  thriven  well  on  cow*s  milk  during 
the  first  fortnight,  but  had  since  been  kept  rather  thin  by  repeated 
attacks  of  what  was  thought  to  be  dyspeptic  vomiting,  was  found 
to  have  a  large  easily  felt  pylorus  and  extremely  well-marked 
visible  peristalsis.  The  recent  feeding  having  been  unsuitable  in 
quality  and  excessive  in  amount,  measured  quantities  of  dilute 
peptonised  milk  were  ordered.  Stomach-washing  was  also  recom- 
mended; but,  for  some  reason,  was  not  carried  out.  With  this  simple 
dieting  and  no  other  treatment,  the  child  soon  ceased  to  vomit,  and 
began  almost  at  once  to  gain  weight  at  the  rate  of  4  ounces  in  the 
week;  she  is  now  a  strong,  healthy  schoolgirl.  In  most  of  these 
cases,  however,  stomach-washing  is  necessary  as  well  as  dieting. 

The  symptoms  in  the  mild  cases  differ  only  in  degree  from  those 
in  the  severe  ones  and  the  physical  signs  are  also  the  same,  although 
they  may  be  longer  in  appearing.  The  condition  of  the  pylorus  and 
stomach  in  the  few  instances  in  which  I  have  seen  them,  either  post- 
mortem or  during  an  operation,  were  also  practically  the  same. 
The  mildness  of  the  clinical  manifestations,  therefore,  probably 
depends  not  on  the  pyloric  muscle  being  less  hypertrophied  than  in 
the  worse  cases,  but  on  its  being  less  frequently  in  a  state  of  abnormal 
contraction,  so  that  it  allows  a  fair  amount  of  food  to  pass  into 
the  bowel. 

Diagnosis.  Only  in  rare  instances  of  the  acute  type  can  a  satis- 
factory diagnosis  of  pyloric  hypertrophy  be  made  from  the  sympn 
toms  alone.  Ordinarily  we  cannot  recognise  the  nature  of  the  case 
with  certainty  until  we  have  observed  exaggerated  visible  peri- 
stalsis, or  made  out  the  enlargement  of  the  pylorus  by  palpation. 
In  doubtful  cases  we  should  also  use  a  stomach-tube  to  find 


CONGENITAL  HYPERTROPHY  OF  PYLORUS      1019 

out  whether  a  measured  quantity  of  food — such  as  2  ounces  of 
diluted  and  peptonised  milk — when  introduced  into  the  stomach 
and  retained  for  three  or  four  hours,  remains  undiminished  in 
amount. 

Exaggerated  visible  peristalsis  occurring  in  a  young  baby,  if 
it  is  really  well-marked  and  forcible  and  accompanied  by  the  charac- 
teristic vomiting  and  other  symptoms,  is  always,  so  far  as  my 
experience  goes,  pathognomonic  of  the  disease.  It  is  most  com- 
monly seen  for  the  first  time  during  the  fourth  or  fifth  week,  and 
is  very  rare  indeed  before  the  end  of  the  third.  Often,  it  begins  much 
later,  and  it  may  go  on  vigorously  after  the  vomiting  has  ceased. 
At  first,  it  may  only  appear  irregularly  at  intervals  of  hours  or  even 
of  days. 

The  large  hard  pylorus  can  often  be  felt  some  time  before  the 
visible  peristalsis  has  begun,  but  in  none  of  my  cases  was  it  made 
out  for  certain  before  the  eighteenth  day  of  life.  The  organ  some- 
times lies  too  deeply  under  the  liver  to  be  felt  even  during  anaes- 
thesia; and,  although  it  is  in  an  accessible  position,  it  may  not  be 
p)ossibIe  to  make  sure  of  its  presence  unless  it  is  in  a  state  of  con- 
traction at  the  time  of  examination.  I  have  never  found  it  necessary 
to  use  x-ray  examination  as  an  aid  in  the  diagnosis  of  this  disease. 

The  cases  which  are  most  apt  to  be  mistaken  for  pyloric  hj'per- 
trophy  are  those  of  an  obscure  nervous  condition  which  has  been 
usually  referred  to  as  "pyloric  spasm."  Mild  instances  of  this 
malady  are  not  uncommon  and  generally  give  little  trouble,  because 
the  vomiting  and  other  symptoms  are  much  less  severe  than  those 
in  pyloric  hypertrophy,  and  generally  subside  rapidly  when  the 
feeding  is  regulated  and  the  stomach  washed  out.  In  a  few  of  the 
cases,  however,  the  symptoms  are  extraordinarily  obstinate  and, 
in  these,  the  diagnosis,  and  especially  the  treatment,  may  be  very 
troublesome. 

The  worst  cases  I  have  seen  have  generally  been  in  girls,  and 
it  is  characteristic  of  the  condition  that  the  child  often  cries  a  great 
deal  as  if  in  pain,  which  children  with  pyloric  hypertrophy  rarely 
do.  The  vomiting  usually  begins  soon  after  birth,  but  does  not 
become  projectile  until  some  time  between  the  end  of  the  second 
and  the  sixth  week.  Its  character  diflfers  somewhat  from  that  in 
pyloric  hypertrophy.  It  generally  occurs  after  each  feeding,  and  the 


1020     CONGENITAL  HYPERTROPHY  OF  PYLORUS 

whole  stomach  contents  are  either  forcibly  rejected  at  once,  or  the 
organ  is  emptied  by  successive  less  severe  efforts.  When  the  stomach- 
tube  is  used  after  vomiting  has  taken  place,  little  or  no  residue  of 
food  is  found  in  the  stomach,  and  there  is  no  evidence  of  gastric 
dilatation  or  hypertrophy.  Occasionally,  before  vomiting  occurs, 
the  outline  of  the  stomach  stands  out  distinctly,  but  it  never 
shows  the  characteristic  vigorous  peristalsis.  The  motions  and  the 
urine  are  usually  scanty,  but  slight  attacks  of  diarrhoea  are  quite 
common. 

The  treatment  of  these  cases  requires  the  greatest  care  and  per- 
severance. Suitable  regulation  of  the  diet  is,  of  course,  necessary, 
and  stomach-washing  should  be  regularly  carried  out;  but  often 
neither  the  one  nor  the  other  has  any  strikingly  beneficial  effect  on 
the  habitual  return  of  the  meals.  The  most  useful  treatment,  in  my 
experience,  has  been  the  cautious  use  of  tincture  of  opium,  begin- 
ning with  doses  of  m.  -^  and  rapidly  increasing  to  m.  ^V  or  even 
m.  •^.  Under  this  the  vomiting  gradually  stops  and  the  weight  in- 
creases. If  the  mother  is  careful,  the  case  often  does  better  at  home 
than  in  hospital,  and  home  treatment  is  also  preferable  because 
these  cases,  like  those  of  pyloric  hypertrophy,  are  apt  to  die  if  they 
contract  infective  diarrhoea.  On  post-mortem  examination,  the 
pylorus  and  stomach  are  found  to  be  quite  normal. 

Cases  of  congenital  narrowing  of  the  second  part  of  the  duo- 
denum with  saccular  dilatation  of  its  first  portion  are  sometimes 
mistaken  for  pyloric  hypertrophy.  In  this  condition,  visible  gastric 
peristalsis  is  sometimes  seen,  but  it  is  not  very  forcible.  It  may  also 
appear  in  the  first  week  of  life,  which  that  in  pyloric  hypertrophy 
never  does.  The  vomiting,  also,  is  not  forcibly  projectile  and  the 
child  is  feeble,  and  does  not  thrive  well  during  the  first  few  weeks, 
as  cases  of  pyloric  hypertrophy  almost  invariably  do. 

Mortality  with  Different  Forms  of  Treatment  in  Hospital  and  in 
Private  Practice.  Out  of  the  lOO  cases,  42  recovered,  and  58  died 
either  of  the  disease  or  of  complications. 

Operations  were  performed  in  39  cases,  of  these  16  (i.e.,  41  per 
cent)  recovered,  and  23  (i.e.,  59  per  cent)  died.  The  operations  were 
of  various  kinds.  Pylorectomy  and  pyloroplasty  were  done  each  in 
I  case;  and  both  patients  died;  gastro-enterostomy  in  12  chil- 
dren, of  whom  3  recovered  (i.  e.,  25  per  cent) ;  divulsion  of  the  py- 


CONGENITAL  HYPERTROPHY  OF  PYLORUS   1021 

lonis  (Loreta's  operation)  in  18,  with  7  recoveries  (i.  e.,  38.9  per 
cent) ;  in  2  others,  Loreta's  operation  failed  to  relieve  the  symptoms 
and  was  therefore  followed  by  gastro-enterostomy,  after  which 
both  patients  made  a  good  recovery;  simple  division  of  the  pylorus 
muscle,  without  stitching  (Rammstedt's  operation)  was  done  in  5 
cases,  with  4  recoveries  (i.e.,  80  per  cent).  The  cases  which  recovered 
were  all  operated  on  by  Sir  Harold  Stiles,  with  the  exception  of 


Nos.  95  and  97,  in  which  the  operations  were  performed  by  Mr.  A. 
P.  Mitchell  and  Mr.  John  Eraser  respectively. 

Of  the  61  cases  in  which  no  operation  was  done,  i  (No.  96)  died 
a  few  days  after  admission  to  hospital  from  acute  nephritis  of 
unknown  origin,  and  6  others  (Nos.  6,  13,  17,  32,  94  and  100),  who 
were  in  a  state  of  extreme  collapse  when  first  seen,  died  rapidly 
from  exhaustion,  most  of  them  within  forty-eight  hours  and  one  on 
the  fifth  day.  Of  the  remaining  54  cases  that  were  medically  treated, 
26  (i.e.,  48  per  cent)  recovered;  and  28  (i.e.,  52  per  cent)  died.  In 
3  of  the  latter,  death  was  caused  by  infective  diarrhoea. 


1022      CONGENITAL  HYPERTROPHY  OF  PYLORUS 


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1028  CONGENITAL  HYPERTROPHY  OF  PYLORUS 


The  most  remarkable  thing  about  the  mortality  statistics  is  the 
striking  difference  between  the  results  obtained  in  hospital  and 
those  in  private  practice.  For  we  find  that  the  total  mortality  of  the 
28  hospital  cases  which  were  operated  on  was  75  per  cent  (21 
deaths),  and  that  of  the  11  private  cases  18.2  per  cent  (2  deaths). 
In  the  same  way,  if  we  exclude  the  7  cases  which  died  within  a 
few  days  of  being  first  seen  and  before  the  treatment  could  be 


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properly  begun,  we  find  that  while  the  31  hospital  cases  which  were 
medically  treated  show  a  mortality  of  74.2  per  cent  (23  deaths), 
that  of  the  23  cases  similarly  dealt  with  in  private  practice  was 
only  21.7  per  cent  (5  deaths). 

There  are  at  least  three  obvious  reasons  for  this  great  difference. 
The  first  of  these  is  the  state  of  debility  in  which  many  of  the  hospital 
cases  were  on  admission,  owing  to  previous  injudicious  feeding. 
This  had  set  up  gastric  catarrh  and  dilatation,  sometimes  with  diar- 
rhoea, and  had  lowered  the  child's  resistance.  In  former  years,  the 
nature  of  the  case  had  rarely  been  recognised  before  the  patient 


CONGENITAL  HYPERTROPHY  OF  PYLORUS      1029 

was  brought  to  the  hospital.  The  second  is  the  danger  of  infective 
diarrhoea,  which  sometimes  occurs  in  hospital  and  practically  never 
in  private  practice.  The  third  reason  is  that  it  is  seldom  possible  to 
give  anything  like  the  same  amount  of  medical  and  nursing  atten- 
tion to  the  hospital  cases  as  in  private  practice.  In  the  latter,  one 
has  usually  been  .able,  when  the  case  was  a  severe  one,  to  arrange  for 
the  child  to  be  looked  after  both  by  day  and  at  night  by  specially 


competent  nurses, who  have  given  their  whole  time  and  attention 
to  him.  I  have  also  made  a  point  of  doing  the  washing  out  of  the 
stomach  myself  or  having  it  done  by  another  medical  man.  This  I 
believe  to  be  important,  for  it  not  only  results  in  the  washing-out 
being  better  done,  but  also  often  in  information  being  obtained 
which  may  be  most  helpful  in  the  regulation  of  the  diet.  If  the 
lavage  is  carried  out  by  nurses,  I  am  convinced  that  this  may 
considerably  lessen  the  chance  of  the  child's  recovery. 

Condition  in  AJter-liJe  of  the  Patients  who  Recover.  Of  the  42 
children  who  recovered,  5  (Nos.  15,  20,  46,  60  and  78)  have  since 


1030  CONGENITAL  HYPERTROPHY  OF  PYLORUS 

died  from  various  causes,  and  4  (Nos.  30,  41,  48  and  68)  who  were 
doing  well  when  last  seen,  have  been  lost  sight  of.  During  January 
and  February  of  this  year  I  have  been  able  to  see  a  number  of  the 
remaining  33  patients  and  have  had  reports  on  all  the  others,  either 
from  their  medical  attendants  or  from  relatives.  The  present  ages 
of  these  children  vary  from  ten  months  to  16^  years.  The  majority, 
doubtless  owing  to  the  extra  care  which  their  mothers  have  taken 
of  them,  are  above  the  average  in  development  and  vigour;  none 
shows  any  signs  of  serious  gastric  derangement.  Apparently  the 
danger  to  hfe  and  even  to  health  in  this  disease  is  only  temporary, 
and  children  who  survive  it  in  infancy  are  in  no  way  handicapped 
thereby  in  after-life.  Those  who  were  operated  on  are  now  apparently 
as  well  as  the  others  who  were  medically  treated. 

Mr.  J.  H.  NicoII  allows  me  to  mention  that  Dr.  John  Ritchie's 
patient,  on  whom  he  performed  Loreta's  operation  in  1899,  and 
who  was  the  first  successful  case  of  operation  for  this  disease  in 
Great  Britain  (3),  was  examined  for  the  Army  last  year  and  passed 
as  A  I. 

BIBLIOGRAPHY 

1.  "On  Defective  Co-ordination  in  Utero  as  a  Probable  Factor  in  the 

Causation  of  Certain  Congenital  Malformations."  Brit.  M.  J.,  II,  678. 

2.  Brit.  M.  J.,  1895,  II,  711,  and  Edinb.  Hosp.  Rep.,  1896,  IV.  116. 

3.  Brit.  M.  J.,  1900,  II,  571. 


THE  CARDIOVASCULAR  DEFECTIVE 
By  Louis  M.  Warfield,  A.B.,  M.D.,  Milwaukee,  Wis. 

THE  examination  of  thousands  of  young  men  for  military 
service  during  the  late  war  has  drawn  attention  to  a  group 
of  symptoms  following  exertion  of  the  slightest  kind,  known 
by  such  synonyms  as  effort  syndrome,  irritable  heart,  neuro-circu- 
latory  asthenia,  etc.  The  English  tagged  their  cases  from  the 
"front"  D.A.H.  (disordered  action  of  the  heart),  but  as  time  went 
on  it  became  evident  that  attention  thus  drawn  to  the  heart  made 
the  victims  worse,  so  that  Thomas  Lewis  proposed  the  name 
"eflfort  syndrome."  The  cases  which  were  invalided  from  the  front 
and  those  seen  in  civil  life  have  the  same  syndrome.  The  difiference, 
if  any,  is  one  of  degree.  It  is  to  the  class  of  cases  seen  in  civil 
life  that  the  name  "cardiovascular  defective"  is  given  in  this 
paper. 

Certain  characteristic  symptoms  are  found  in  all  cases  of  the 
cardiovascular  defective.  These  are  symptoms  from  which  many 
men  suffer  when  put  through  violent  exertion.  The  differentiation 
between  the  defectives  and  the  normal  men  is  largely  one  of  degree. 
Exercise  of  the  lightest  character  serves  to  bring  out  in  the  defectives 
an  exaggeration  of  all  the  symptoms  of  exhaustion.  Typically,  after 
sHght  exertion  the  men  become  breathless,  giddy,  have  pain  over 
the  precordium,  palpitation  of  the  heart,  and  have  a  feeling  of  utter 
exhaustion.  Frequently  they  have  headache,  are  sleepless,  rest  at 
night  really  does  not  rest  them,  and  they  have  clammy  cyanosed 
hands  and  feet.  They  sweat  profusely  in  the  axillae  and  have  a 
mottled  skin  and  unstable  vasomotor  reaction. 

This  train  of  symptoms  follows  practically  every  serious  illness 
and  lasts  for  a  long  or  short  time,  depending  upon  the  recupera- 
tive powers  of  the  person  affected  and  uf)on  the  severity  of  the  ill- 
ness. This  is  to  be  expected  and  causes  no  anxiety.  It  is  only  when  the 
time  has  passed  that  recovery  should  be  perfect  and  symptoms  still 

103 1 


1032  THE  CARDIOVASCULAR  DEFECTIVE 

persist  that  permanent  damage  to  the  cardiovascular  system  may  be 
suspected. 

With  us  at  JeflFerson  Barracks,  Missouri,  an  attempt  was  made 
to  cull  out  these  defectives  before  they  were  taken  into  the  service. 
We  were  not  wholly  successful  in  that  certain  men,  who  were  exam- 
ined before  we  fully  appreciated  the  condition  and  who  apparently 
were  normal,  later  were  admitted  to  hospital  with  the  characteristic 
symptoms.  These  men  had  developed  the  symptoms  under  the  set- 
ting-up exercises  and  comparatively  light  military  duty  given  them 
at  this  post.  Certain  men,  thought  by  us  to  be  border-line  cases, 
given  the  benefit  of  the  doubt  and  accepted,  also  later  were  admitted 
to  the  hospital. 

Tachycardia  is  known  to  be  produced  by  a  variety  of  conditions. 
Hence  at  the  final  examination  in  the  Examining  Barracks  by  the 
two  members  of  the  special  board,  the  tuberculosis  and  cardio- 
vascular examiners,  cases  were  sorted  into  several  categories. 
Some  were  frankly  tuberculosis  and  were  at  once  rejected.  Some 
were  cases  of  exophthalmic  goiter,  of  definite  hyperthryoidism,  of 
cirrhosis  of  the  liver,  chronic  malaria  with  enlarged  spleen,  bron- 
chial asthma,  etc.,  and  were  at  once  rejected.  There  were,  however, 
others  which  could  not  be  so  summarily  dealt  with.  These  were 
cases  in  which  tachycardia  or  very  labile  pulse  was  found,  and  in 
whom  no  definite  lesion  of  any  kind  could  be  discovered.  These 
men  were  sent  to  the  hospital  for  further  observation  and  exam- 
ination. 

After  careful  examination  the  men  were  placed  in  squads  and 
daily  exercised  with  mild  setting-up  exercises  under  the  charge  of 
a  non-commissioned  officer  who  had  been  schooled  in  the  drill. 
The  exercises  recommended  by  Lewis  were  used.  His  C^^  and  D^° 
were  given,  supplemented  by  hikes  of  varying  distances,  and  periods 
of  double-quick.  Temperature  readings  and  pulse  rates  were  taken 
on  all  patients  every  three  hours.  Exercise  was  so  timed  that  the 
3  P.M.  readings  were  taken  from  twenty  minutes  to  half  an  hour 
after  exercise.  In  this  manner  we  studied  over  400  cases  referred 
from  the  heart  and  lung  room  in  the  Examining  Barracks.  Many 
of  these  proved  to  be  simple  excitement  tachycardia  and  no  record 
was  kept  of  them.  We  studied  carefully  315  cases  and  exercised  158 
in  hospital.  In  297  the  records  were  complete  enough  for  later  use. 


THE  CARDIOVASCULAR  DEFECTIVE  1033 

Disposition  oj  Cases  at  Examining  Barracks 

60  cases  (37  per  cent)  diagnosed  hyperthyroidism Rejected 

47      "      (29  per  cent)  "         pulmonary  tuberculosis. .  . .  Rejected 

52      "     (32  per  cent)  "         irritable  heart Rejected 

2      "     (1.2  per  cent)         "         cirrhosis  of  the  liver Rejected 

1  case   (  .8  per  cent)         "        bronchial  asthma Rejected 

Disposition  of  Cases  Observed  in  Hospital 

40  cases  (29.6  per  cent)  no  lesion  found,  normal Accepted 

17     "     (12.6  per  cent)  diagnosed  hyperthyroidism Rejected 

47      "      (34-8  per  cent)           "        pulmonary  tuberculosis .  .  Rejected 
29      "     (21.5  per  cent)  "        irritable  heart Rejected 

2  "     (1.5  per  cent)  "        cirrhosis  of  the  liver Rejected 

It  will  be  seen  that  cases  of  pulmonary  tuberculosis  and  hyper- 
thyroidism (including  exophthalmic  goiter)  composed  the  greater 
proportion  of  the  two  groups.  As  a  matter  of  fact  the  symptoms 
complained  of  by  men  are  so  similar  in  the  cases  of  diseases  named 
above  and  irritable  heart  that  it  is  only  after  the  most  careful 
study  that  the  cases  can  be  separated  into  the  proper  group. 

Our  cases  of  irritable  heart,  the  cardiovascular  defective,  fall 
into  three  groups: 

(A).  Strictly  Cardiovascular. 

1 .  Following  infectious  disease.  Chronic  myocardial  degenera- 

tion. 

2.  Existing  since  childhood. 

(a)  Associated  with  poor  mentality. 
(6)  Associated  with  good  mentahty. 

(B).  Some  defect  in  endocrine  secretion. 

1.  Hyperthyroidism. 

2.  Exophthalmic  goiter. 

(C).  Associated  with  definite  somatic  lesions. 

1.  Pulmonary  tuberculosis. 

2.  (Hodgkin's  disease). 

3.  Focal  infections,  chronic. 

4.  Other  diseases,  cirrhosis  of  liver  (hookworm)  asthma,  etc. 


1034  THE  CARDIOVASCULAR  DEFECTIVE 

(A)  The  following  case  is  typical  of  the  first  group,  Subsection  i : 

Case  XXI.  A.  W.  S.,  recruit  aged  twenty-seven,  a  farmer.  His  father 
died  of  cancer  of  the  stomach.  His  mother  is  living,  but  is  nervous.  She 
has  heart  trouble  and  rheumatism.  He  has  three  half-brothers,  one  half- 
sister,  children  of  same  father.  All  are  well.  His  mother  was  thirty-four 
years  old  when  he  was  born.  He  went  through  the  country  school,  but  did 
not  pass  in  all  branches.  Can  read,  write,  spell,  compute  fractions.  He 
left  school  at  the  age  of  sixteen,  has  worked  on  a  farm  since.  Has  worked 
hard  and  up  to  five  years  ago  had  never  been  ill.  At  that  time  he  had 
rheumatism,  evidently  articular,  which  lasted  for  three  months.  He  has 
never  since  that  time  been  able  to  work  hard.  About  one  year  ago  he  had 
"heat  stroke."  Since  then  he  tires  even  more  easily,  has  palpitation  of  the 
heart,  gets  dizzy  and  short  of  breath  on  slight  exertion.  The  patient  is 
tall,  a  healthy-looking  and  well-muscled  man.  Pulse  sitting,  94,  very  labile. 
Hops  90  times  on  one  foot  and  then  is  exhausted,  dizzy.  Pulse  is  142, 
regular.  He  is  breathless,  has  no  pain.  Two  minutes  later  pulse  112.  The 
apex  beat  is  in  the  5th  i.s.  7.5  cm.  from  the  m.s.I.  Heart  sounds  are  clear. 
The  pulmonic  second  is  accentuated.  Diagnosis:  irritable  heart,  caused 
by  acute  articular  rheumatism  resulting  in  myocardial  weakness. 

This  case  seems  to  have  followed  a  severe  attack  of  articular 
rheumatism,  although  the  sunstroke  was  claimed  to  have  made  the 
man  more  easily  exhausted.  We  have  had  several  such  cases.  All 
occurred  in  farmer  boys  and  all  dated  their  symptoms  from  the  sun- 
stroke. If  sunstroke,  as  claimed  by  some,  is  an  infection,  then  the 
cases  of  effort  syndrome  following  this  cause  must  be  classed  as 
myocardial  in  character. 

Cases  belonging  to  the  second  subgroup  of  the  first  Group  (A) 
are  those  which  come  strictly  under  the  heading  of  cardiovascular 
defectives.  In  them  no  cause  whatever  can  be  discovered.  They 
represent  a  class  which  has  had  a  bad  start  in  life.  Tracing  the 
family  history  reveals  nervous  instability  on  the  part  of  one  or  both 
parents,  alcoholism,  or  insanity.  Often  the  mother  is  beyond  the 
age  of  thirty  when  the  boy  was  born.  So  many  come  from  the  farmer 
class  that  it  would  appear  to  be  some  environmental  factor  either 
affecting  parents  or  child,  or  both,  which  produces  tissues  poor  in 
resistance.  These  boys  lack  ambition.  They  do  not  think  much 
about  afi'airs  in  general.  The  work  they  do  is  desultory.  Whenever 
they  feel  tired  they  stop  for  a  while  and  rest.  Such  cases  have  had 


THE  CARDIOVASCULAR  DEFECTIVE  1035 

little  schooling.  Some  appear  stupid  from  lack  of  opportunity,  but 
the  stupidity  for  the  most  part  is  that  of  mentality  ot  a  low 
order,  and  apparent  underdevelopment  of  the  brain.  Such  a  case 
is  the  following: 

Case  IX.  H.  C,  recruit  aged  twenty-one  years,  a  farmer,  has  a  family 
history  negative  as  to  nervousness  or  any  insanity.  He  had  very  little 
schooling,  the  history  showing  that  he  was  not  particularly  bright.  In 
the  hospital  here  he  appeared  so  subnormal  mentally  that  he  was  sent 
to  the  psychiatry  staff  for  examination.  Nothing  definite  was  found  except 
slow  cerebration.  His  complaint,  dating  back  several  years,  was  of  breath- 
lessness  on  exertion,  exhaustion,  and  pain  over  heart.  He  was  also  nervous 
and  unable  to  sleep  at  night.  He  stood  the  graded  exercises  poorly.  He 
never  drilled  since  entering  the  army  February  25,  1918.  Physical  examina- 
tion negative  except  for  rapid  heart.  Apex  beat  within  nipple  line.  Cannot 
hop  100  times.  Pulse  before  exercise,  108;  after  exercise,  160.  In  two 
minutes  still  rapid,  130.  Dizziness,  exhaustion,  and  breathlessness  com- 
plained of.  Diagnosis:  irritable  heart.  Recommended  for  Surgeon's  Certifi- 
cate of  Disability. 

The  other  class  of  case  in  this  subgroup  exhibits  the  same 
symptoms  physically,  but  the  mentality  is  above  the  average.  It 
is  no  lack  of  opportunity  for  education  in  such  cases  illustrated 
above,  but  a  real  lack  of  ability  to  learn.  This  actually  has  no  par- 
ticular bearing  upon  the  train  of  symptoms  exhibited  by  these  men. 
It  only  serves  to  group  them  into  the  two  classes,  in  either  one  of 
which  the  same  syndrome  is  brought  out  on  slight  exertion.  The 
man  with  subnormal  mentality  necessarily  never  gets  beyond  a 
certain  low  scale  in  community  life.  His  capabilities  are  necessarily 
so  limited  and  his  physical  disability  is  so  great  that  he  has  not  the 
will  to  overcome  his  physical  defects  and  force  his  brain  to  act.  In 
the  struggle  for  existence  he  can  just  keep  himself  above  water. 
The  man  of  the  other  class  finds  better  living  conditions  and  better 
pay  provided  he  can  obtain  a  position  which  supports  him  without 
the  necessity  of  physical  exertion.  Such  a  case  is  the  following: 

Case  XXVI.  L.  C.  B.,  recruit  aged  twenty-five  years,  is  a  clerk  by 
occupation.  His  father  has  had  nervous  headaches  for  years  and  his  mother's 
health  is  only  fairly  good.  He  was  sick  in  bed  for  the  greater  part  of  his 
childhood  because  of  nervousness,  and  missed  a  large  part  of  his  schooling. 


1036  THE  CARDIOVASCULAR  DEFECTIVE 

He  had  no  difficulty  in  learning  when  he  was  in  school.  Five  years  ago 
while  at  a  show  he  became  unconscious  and  remained  in  a  stupor  for 
three  days.  It  was  said  to  be  nervous  prostration.  He  has  always  suffered 
from  headaches  and  has  never  been  able  to  exercise  on  account  of 
exhaustion,  breathlessness,  and  headaches.  He  has  been  able  to  keep  a 
position  as  city  clerk  where  the  work  is  very  light  and  not  very  steady. 
He  is  not  able  to  work  every  day.  On  examination  he  appears  to  be  a  robust 
young  man.  Lungs,  heart,  abdomen,  show  no  abnormalities.  Slight  apical 
cardio-respiratory  murmur  is  present.  Sitting  quietly,  pulse  lOO.  After 
hopping  exercise,  pulse  i6o.  There  was  breathlessness,  sweating  hands, 
precordial  pain,  exhaustion,  dizziness.  Two  minutes  later  pulse  still  fast, 
130.  Blood  pressure  normal.  Diagnosis:  irritable  heart. 

The  second  group,  containing  the  subheadings  hyperthyroidism 
and  exophthalmic  goiter,  is  too  well  known  to  need  extended  com- 
ment. The  symptoms  complained  of  by  these  men  diff'er  only  in 
degree  from  those  presented  by  the  men  with  irritable  heart.  The 
important  point  to  bear  in  mind  is  that  these  cases  besides  having 
tachycardia  have  also  tremor  of  the  extended  fingers,  lagging  of  the 
upper  lids  when  looking  quickly  down,  and  often  poor  convergence  at 
near  vision.  Besides,  as  we  have  shown  elsewhere,  the  blood  pressure 
in  these  cases  is  usually  raised,  whereas  the  blood  pressure  in  the  cases 
of  irritable  heart  is  normal  or  inclined  to  be  slightly  below  normal. 
The  blood  pressure  is  raised  in  the  hyperthyroidism-exophthalmic 
goiter  group,  and  normal  or  below  normal  in  the  strictly  irritable 
heart  group.  Diagnosis  between  these  groups  is  not  always  easy 
nor  is  it  always  possible.  One  competent  examiner  will  classify  a 
case  as  one  of  irritable  heart,  an  equally  competent  examiner  will 
classify  the  same  case  as  hyperthyroidism.  The  distinction  appears 
to  the  writer  to  be  valuable  only  in  so  far  as  the  latter  is  a  potential 
acute  exophthalmic  goiter.  I  do  not  believe  there  is  any  emotional 
shock  violent  enough  to  bring  out  Graves*  disease  in  a  normal  man. 

There  is  one  diff"erence  which  we  discovered  between  the  cases 
of  true  irritable  heart  (eff'ort  syndrome)  and  the  cases  of  hyper- 
thyroidism. That  was  the  response  to  graded  exercise.  The  former 
responded  poorly.  The  latter  were  usually  able  to  perform  the 
setting-up  exercises  up  to  D^**  with  no  subjective  symptoms.  The 
tachycardia  was  often  the  only  sign  of  abnormal  reaction.  Oc- 
casionally the  tremor  of  the  hands  was  increased. 


THE  CARDIOVASCULAR  DEFECTIVE  1037 

Group  C.  In  this  group  are  placed  a  number  of  diseases  which 
cause  in  the  victim  symptoms  so  like  the  effort  syndrome  that 
only  the  most  painstaking  observation  and  examination  will  serve 
to  make  a  correct  diagnosis.  Foremost  among  this  group  of  diseases 
is  pulmonary  tuberculosis  in  the  incipient  stage.  When  patients 
have  largely  symptoms  of  the  absorption  of  tuberculo-toxin  without 
very  definite  physical  findings,  the  problem  of  diagnosis  is  a  difficult 
one.  Our  cases  were  always  examined  by  at  least  two  men  and  they 
were  examined  often  where  any  doubt  existed.  The  men  were  sent 
to  the  hospital  because  of  persistent  tachycardia,  that  being  the 
objective  finding  which  was  most  evident.  They  were  placed  in 
the  group  of  cases  under  observation.  The  temperature,  pulse,  and 
respiration  were  taken  every  three  hours  and  they  were  exercised 
by  the  drill  instructor.  By  this  means  we  were  able  to  sort  out  the 
cases  of  tuberculosis  from  the  other  cases  with  tachycardia  by 
observing  the  rise  in  temperature  following  exercise,  and  the  de- 
velopment or  increase  of  physical  signs.  The  following  case  illustrates 
this  p>oint: 

Case  XV.  L.  L.,  recruit  aged  twenty-two  years;  complaint  of  loss  of 
weight  and  exhaustion  on  sfight  exercise,  with  some  dizziness  and  pre- 
cordial pain.  He  had  gradually  developed  these  symptoms  within  six 
months.  His  family  history  was  negative  and  his  past  history  revealed 
no  serious  illnesses.  He  had  always  been  healthy  and  able  to  work.  On 
examination  there  were  slight  signs  of  infiltration  at  the  left  apex.  RHIes 
were  variable.  X-ray  plates  showed  slight  haziness  at  the  left  apex.  There 
was  no  cough,  no  sputum.  Even  the  sHghtest  exercise  caused  him  great 
distress  and  the  temperature  taken  from  twenty  to  thirty  minutes  after 
the  exercise  always  showed  a  rise.  The  morning  temperature  was  sub- 
normal. Frequent  examinations,  the  rapid  temperature  following  exercise, 
and  his  exceedingly  poor  response  to  exercise  led  us  to  the  diagnosis  of 
incipient  pulmonary  tuberculosis.  His  exercise  response  was  far  more 
severe  than  any  of  the  cases  of  irritable  heart. 

I  feel  sure  that  hookworm  disease  and  early  Hodgkin's  disease 
would  show  the  same  effort  syndrome.  I  have  no  case  histories  to 
prove  my  contention.  I  have  only  recollection  of  symptoms  com- 
plained of  in  patients  seen  in  civilian  practice.  Uncinariasis  is  easily 
diagnosed.  Early  Hodgkin's  disease  is  not  so  easily  detected. 

Chronic  focal  infections  also  may  show  typical  effort  syndrome. 


1038  THE  CARDIOVASCULAR  DEFECTIVE 

I  have  observed  no  cases  in  my  studies,  but  I  agree  with  those  who 
make  this  assertion.  I  have  not  seen  the  removal  of  tonsils  or  the 
opening  of  nasal  sinuses  or  the  cleaning  of  apical  tooth  abscesses 
cure  cases  which  had  the  eflFort  syndrome,  although  I  have  no  doubt 
that  such  cases  do  occur  and  such  pathological  conditions  should 
always  be  kept  in  mind  so  that  gross  errors  in  diagnosis  are  avoided. 
I  have  seen  bronchial  asthma,  cirrhosis  of  the  liver,  and  chronic 
malaria  in  patients  who  had  eflfort  syndrome  and  tachycardia.  These 
patients  were  much  improved  under  treatment.  Those  with  the  last- 
named  disease  went  back  to  duty. 

Etiology.  We  do  not  know  why  certain  healthy,  even  robust- 
looking  men  have  this  strange  inability  to  respond  as  normal  per- 
sons do  to  a  slight  amount  of  physical  exertion.  They  are  always  in 
the  condition  of  a  normal  man  just  convalescing  from  a  severe  ill- 
ness. No  wonder  that  they  lack  ambition  to  overcome  obstacles, 
and  are  passed  in  the  race  of  life.  In  the  history  of  the  cardiovascular 
defective  certain  points  may  be  emphasized.  The  first  is  the  parental 
history.  These  men  do  not  have  a  fair  start.  One  or  both  parents 
suffered  from  nervousness,  chronic  headaches,  insanity,  or  were 
alcoholic  in  §§  per  cent  of  the  cases.  Practically  all  the  men  dated 
their  symptoms  into  childhood.  "As  long  as  I  can  remember'*  was 
a  frequent  response  to  the  question,  "How  long  have  you  had  these 
symptoms?"  In  only  50  per  cent  of  my  cases  was  there  a  definite 
time  set  which  followed  some  infectious  disease.  The  other  50  per 
cent  could  set  no  time  of  onset,  nor  could  they  say  that  infectious 
disease  had  any  relation  to  the  symptoms.  The  fact  that  so  many 
of  these  defectives  come  from  a  neurotic  parentage  and  are  brought 
up  in  an  environment  surcharged  with  bodily  complaints  renders 
them  introspective  of  their  small  ailments.  Eventually  their  mental 
states  so  dominate  the  somatic  functions  that  trivial  sensations  are 
magnified  to  an  extent  which  causes  them  acute  suffering.  Should 
this  take  the  form  of  palpitation  of  the  heart,  sensible  to  them,  and 
should  some  doctor  tell  them  they  have  heart  disease  and  treat 
them  for  it,  the  cases  become  practically  helpless  hypochondriacs. 
The  following  is  illustrative  of  this  group: 

Case  XXX.  F.  C.  J.,  recruit  aged  twenty-five  years,  was  a  big,  healthy 
fellow,  but  always  had  a  worried  look.  He  entered  the  army  at  this  post 
July  II,  1918,  admitted  to  the  hospital  July  16.  His  mother  was  neurotic,  a 


THE  CARDIOVASCULAR  DEFECTIVE  1039 

fussy  woman;  his  father  was  well.  Several  brothers  and  sisters  were  all 
well.  As  a  child  his  mother  said  he  was  always  nervous,  never  could  play 
with  the  other  children  as  he  became  easily  exhausted.  He  was  evidently 
nagged  during  his  youth.  When  he  was  old  enough  to  work  he  was  taken 
away  from  one  position  after  another  as  soon  as  he  made  any  com- 
plaint. Finally,  about  four  years  ago,  his  mother  took  him  to  a  doctor, 
who  told  him  he  had  serious  heart  disease  and  treated  him  for  it  up  to 
the  time  he  was  drafted  into  the  army.  He  was  married  and  was  supported 
by  his  wife  and  mother.  He  could  not  do  any  work.  He  complained  of 
inability  to  perform  even  the  slightest  exercise.  He  was  obsessed  with  the 
idea  that  he  had  serious  heart  trouble,  his  mother  and  wife  abetting  him 
in  this  belief.  On  slight  exertion,  heart  pounded,  he  had  precordial  pain, 
dizziness,  headache,  breathlessness,  and  exhaustion.  On  physical  examina- 
tion he  was  tall,  well  built,  and  a  strong-looking  man.  The  pulse  was  always 
rapid.  The  heart  was  slightly  enlarged.  There  was  a  soft,  short  systolic 
murmur  at  the  apex  not  considered  to  be  organic.  The  lungs  were  negative. 
The  blood  pressure  was  116-80.  Exercise  response  was  poor.  There  was 
rapid  pulse,  pounding  heart,  and  anxious  expression.  The  vasomotor  in- 
stability was  marked.  Diagnosis:  irritable  heart,  hypochondriasis. 

Frequently  in  the  histories  of  these  cardiovascular  defectives 
there  will  be  fainting  spells,  attacks  of  dizziness,  when  everything 
gets  black,  or  there  will  be  convulsive  seizures  and  unconscious 
periods  lasting  for  hours  or  days.  Attacks  of  nervous  prostration 
in  children  are  not  uncommon.  Such  abnormal  conditions  can  only 
occur  on  a  marked  neuropathic  basis.  The  cases  which  date  their 
symptoms  from  some  infectious  disease  have  not  given  such  his- 
tories. They  complain  only  of  the  symptoms  which  follow  exertion 
and  which  they  are  certain  were  not  present  previous  to  the  illness. 
In  these  cases  one  may  feel  reasonably  sure  that  the  myocardium 
has  been  permanently  damaged.  Dilatation  of  the  heart  following 
slight  exertion  will  account  for  all  the  symptoms  of  the  effort 
syndrome. 

Where  no  cause  can  be  assigned  we  are  forced  back  upon  the 
term  "constitutional  inferiority,"  which  explains  nothing.  It  simply 
states  a  fact  with  which  all  are  familiar. 

Graded  Exercise.  Graded  setting-up  exercises  were  begun  with 
the  idea  of  hardening  the  men  so  that  they  could  do  full  duty.  It 
was  thought  that  a  certain  number  of  men  with  the  effort  syndrome 
could  be  gradually  strengthened.  Before  the  cases  were  fully  recog- 


1040  THE  CARDIOVASCULAR  DEFECTIVE 

nized  at  the  Examining  Barracks  some  men  were  accepted  who  had 
mild  symptoms  with  slight  tachycardia  at  rest.  These  men  were 
put  out  at  the  usual  setting-up  exercises.  Some  fainted,  some  grew 
so  dizzy  that  they  had  to  be  excused,  some  managed  to  get  through 
a  day's  exercise,  but  were  exhausted  and  bed-ridden  for  the  next 
day  or  two.  Hence  it  was  felt  that  a  more  gradual  break-away  from 
their  sedentary  civilian  lives  would  render  these  men  less  liable  to 
break  down  under  violent  exercise.  In  this  we  were  disappointed. 
In  no  case  of  true  effort  syndrome  was  there  any  betterment  even 
after  days  of  the  slightest  exercise.  Any  attempt  to  go  from  very 
light  to  a  light  exercise  brought  on  symptoms  more  violent  than 
before.  On  the  other  hand,  there  were  cases  diagnosed  irritable  heart 
at  the  Examining  Barracks  who  were  accepted  for  Limited  Service. 
Two  months  later  at  the  examination  for  demobilization  many  of 
these  men  had  normal  cardiovascular  response  to  exercise.  In  every 
case  where  the  condition  had  apparently  cleared  there  were  abso- 
lutely no  symptoms  complained  of  at  any  time  in  the  man's  life 
except  the  pounding  of  the  heart  following  violent  exertion  in  men 
who  were  unaccustomed  to  exercise.  They  were  clerks  or  others 
who  led  sedentary  lives.  On  the  contrary,  the  cases  which  still 
revealed  the  effort  syndrome  were  those  who  had  complained  of 
precordial  pain  or  dizziness,  with  the  pounding  heart  after  exercise 
and  previous  to  their  induction  into  service.  These  men  without 
exception  stated  that  they  had  not  been  able  to  stand  the  light  drill 
and  had  been  working  the  past  two  months  as  clerks.  This  lends 
weight  to  the  point  that  in  the  history  of  the  man  there  must  be  one 
or  more  of  the  cardinal  symptoms  of  the  syndrome.  The  tachy- 
cardia alone  is  not  sufficient  for  diagnosis.  The  pulse  may  remain 
rapid  longer  than  two  minutes  after  the  usual  test  exercise  of  hopn 
ping  100  times  on  one  foot.  There  may  even  be  great  exhaustion 
present,  but  if  there  have  been  no  symptoms  which  careful  inquiry 
has  elicited,  one  is  not  justified  in  diagnosing  the  case  irritable 
heart. 

The  temperature  of  every  patient  was  taken  twenty  minutes 
after  exercise.  The  cases  of  pulmonary  tuberculosis  could  be  picked 
out  by  the  temperature  reaction.  All  the  men  exercised  were  those 
up>on  whom  a  definite  diagnosis  had  not  been  made.  It  was  found 
that  cases  could  be  sorted  into  groups  according  to  their  response 


THE  CARDIOVASCULAR  DEFECTIVE  1041 

to  exercise.  For  example,  the  cases  of  suspected  hyperthyroidism 
responded  best  to  exercise.  The  pulse  rate  was  not  so  high,  there 
was  no  rise  of  temperature,  and  symptoms  were  not  so  severe  as  a 
rule.  Further,  they  often  were  able  to  increase  exercise  without  dis- 
comfort. The  cases  of  eflFort  syndrome  showed  no  improvement 
under  exercise.  They  often  grew  worse  and  had  to  be  excused.  The 
temperature  was  not  raised  in  these  men.  The  cases  of  suspected 
pulmonary  tuberculosis  usually  responded  badl}'^  to  exercise.  They 
became  easily  exhausted,  showed  marked  breathlessness.  The  tem- 
perature was  always  raised  from  10  to  30  after  exercise  and  there 
were  frequently  rales  heard  over  one  or  both  apices  where  none  had 
been  heard  before.  Graded  exercise,  therefore,  is  not  only  of  thera- 
p>eutic  value,  but  it  becomes  of  real  diagnostic  value  under  certain 
circumstances.  Further,  in  the  cases  of  effort  syndrome  where  the 
symptoms  dated  definitely  from  some  serious  illness,  often  ten  to 
fifteen  years  previously,  there  was  frequently  demonstrable  an  actual 
displacement  of  the  apex  beat  to  the  left  following  the  exercise.  This 
could  have  but  one  meaning  and  hence  was  interpreted  as  dilatation 
of  the  left  side  of  the  heart.  ' 

Prognosis.  As  has  been  stated,  it  has  not  been  possible  for  us  to 
benefit  these  cases  by  graded  exercise.  After  some  experience  with 
the  cardiovascular  defectives  we  rejected  them  after  studying  them 
in  hospital,  in  order  to  be  sure  we  were  making  no  mistakes  in  diag- 
nosis. Those  with  marked  psychoneurotic  state  we  consider  to  be 
hop>eIess  spongers  on  their  families  or  on  the  communities  in  which 
they  live.  For  other  cases  who  have  been  making  a  living  at  farming 
or  clerking,  we  see  no  reason  to  predict  any  bad  fate.  As  long  as 
they  recognize  their  limitations  and  live  always  within  them,  they 
should  have  no  diflficulty  in  keeping  well  and  free  from  distressing 
symptoms,  chiefly  palpitation  and  precordial  pain. 


A  CASE  OF  AYERZA'S  DISEASE: 

CHRONIC  CYANOSIS,  DYSPNEA,  AND  ERYTHREMIA,  ASSOCIATED 
WITH  SYPHILITIC  ARTERIOSCLEROSIS  OF  THE  PULMONARY 
ARTERIES 

By  Aldred  Scott  Warthin,  Ph.D.,  M.D., 

Professor  of  Pathology  and  Director  of  Pathological  Laboratories,  University  of  Michi- 
gan, Ann  Arbor,  Mich. 

THE  discovery  by  Vaquez,  in  1892,  of  the  syndrome  of  chronic 
cyanosis,  persistent  polycythemia,  and  enlargement  of  liver 
and  spleen,  in  the  absence  of  organic  heart  involvement,  and 
Osier's  service  later  in  calling  the  attention  of  the  medical  profession 
to  this  new  complex,  established  a  definite  place  for  it  in  nosology 
as  Vaquez's  disease.  Osier's  disease,  Osler-Vaquez  disease,  ery- 
thremia, primary  polycythemia,  splenomegalic  polycythemia,  poly- 
cythemia with  chronic  cyanosis,  myelopathic  polycythemia,  crypto- 
genic polycythemia,  erythrocytosis  megalosplenica,  etc.  Lucas  (i) 
collected  149  undoubted  and  30  questionable  cases  from  the  liter- 
ature. Since  his  paper  the  number  reported  has  increased  to  over 
200.  Lucas,  in  his  summary,  came  to  the  conclusion  that,  in  the  light 
of  the  present  knowledge  of  the  disease,  it  was  difficult  to  estab- 
lish a  hard-and-fast  line  between  cases  of  polycythemia,  probably 
secondary  in  form  but  of  obscure  origin,  on  the  one  hand,  and 
unquestionable  cases  of  primary  polycythemia  or  erythremia  on 
the  other.  The  23  reported  autopsies  had  thrown  but  little  light 
on  this  question. 

Since  Lucas'  paper  the  question  as  to  the  primary  or  secondary 
nature  of  the  Osier- Vaquez  syndrome  has  received  more  attention, 
and  there  is  an  increasing  number  of  cases  in  which  the  syndrome 
has  been  found  associated  with  other  conditions  in  such  a  way  as  to 
make  it  certain  that  the  symptom-complex  was  purely  secondary. 
The  separation  of  a  primary  polycythemia  from  a  secondary  ery- 
throcytosis has  become  more  difficult,  and  the  question  may  well 
be  asked  if  a  primary  Osier- Vaquez  disease  exists.  The  uncertainty 

1042 


A  CASE  OF  AYERZA'S  DISEASE  1043 

attending  this  question  has  led  recent  writers  to  split  up  the  Osler- 
Vaquez  disease  into  a  number  of  groups.  The  fact  that  cases  are 
reported  under  such  titles,  or  are  classed  as  "  Polycythemia  without 
splenomegaly,"  "Polycythemia  without  cyanosis,"  the  " frustrate 
form,"  congenital  form,  cardiac  form,  "Geisbock's  disease,"  **BIu- 
menthal's  disease,"  etc.,  reveals  the  confusion  attending  the  effort 
to  fix  the  symptom-complex  as  a  distinct  morbid  entity.  Similarly 
the  attempts  to  separate  forms  upon  a  basis  of  the  number  of  red 
cells,  state  of  the  bone-marrow,  etc.,  are  evidence  of  the  difficulty 
in  giving  the  syndrome  a  fixed  position  in  nosology. 

Does  a  primary  erythremia  exist?  The  writer  believes  not, 
certainly  not  in  cases  showing  chronic  cyanosis  and  dyspnea.  Why 
should  a  case  of  pure  or  absolute  polyglobulism  have  either  cyanosis 
or  dyspnea?  On  the  other  hand,  there  is  every  reason  why  a  case  of 
chronic  cyanosis  and  dyspnea  should  develop  a  chronic  erythremia. 
It  is  most  probable  that  all  erythremias  associated  with  cyanosis 
and  dyspnea  (with  a  theoretical  exception  of  a  neoplastic  overforma- 
tion  of  red  cells,  yet  to  be  definitely  shown  to  exist)  are  compensatory 
in  nature  (secondary  to  pulmonary  sclerosis,  emphysema,  congenital 
heart  lesions,  chronic  pulmonary  diseases  leading  to  insufficient 
oxygenation,  increased  resistance  of  the  red  cells  with  lessened 
oxygen-carrying  capacity,  etc.). 

With  this  point  stated,  the  writer  presents  a  unique  case  of  Osler- 
Vaquez  disease,  which  was  under  clinical  observation  for  five  years, 
with  full  autopsy  and  microscopic  findings,  in  which  the  Vaquez 
syndrome  of  chronic  cyanosis,  persistent  high  erythremia,  enlarge- 
ment of  liver  and  spleen,  and  hyperplasia  of  bone-marrow,  are 
shown  to  be  secondary  to  syphilitic  disease  of  the  pulmonary  arteries 
(Ayerza's  disease). 

Case.  L.  H.,  American,  forty-three  (?)  years  of  age,  laborer,  was  ad- 
mitted to  the  Medical  Clinic  (Dr.  George  Dock)  of  the  University  Hospital, 
Ann  Arbor,  January  17,  1907,  and  was  presented  in  the  Clinic  on  the  fol- 
lowing day.  His  chief  complaints  at  that  time  were  difficult  breathing,  pal- 
pitation, blueness  of  skin  and  lips,  general  weakness,  dropsy,  and  frontal 
and  occipital  headaches. 

His  family  history,  as  far  as  known  to  him,  was  negative.  His  father 
was  living;  his  mother  had  recently  had  an  amputation  of  right  tibia  for 
thyroid  metastasis.  He  was  unmarried.  He  denied  venereal  disease,  and 


1044  A  CASE  OF  AYERZA'S  DISEASE 

claimed  to  drink  and  smoke  but  rarely.  His  health  had  been  good  up  to 
about  thirty  years  of  age,  when  he  began  to  have  asthmatic  attacks  at 
night.  These  increased  in  severity  and  frequency.  At  thirty-six  he  had  a 
sudden  attack  of  apnea,  and  was  unconscious  for  several  minutes.  From 
this  time  on  he  had  more  frequent  and  severe  asthmatic  attacks,  at 
irregular  intervals,  usually  at  night.  Four  years  before  entrance  to  the 
hospital  he  first  noticed  blueness  and  swelling  of  his  face,  hands,  and 
feet.  He  was  told  by  a  physician  that  he  had  "heart  trouble,"  and  under 
medical  treatment  his  symptoms  improved;  the  cyanosis  disappeared  and 
did  not  return  until  September,  1906.  From  this  time  on  attacks  of  cyanosis, 
palpitation,  and  dyspnea  became  more  frequent  and  severe,  with  severe 
frontal  headaches,  frequent  dizziness,  prominence  of  eyes,  feeling  of  thoracic 
constriction,  particularly  when  lying  down.  Pressure  upon  sternum  pro- 
duced a  sensation  of  "smothering."  He  had  no  dysphagia,  and  no  marked 
gastrointestinal  disturbances. 

Physical  examinations  by  Drs.  Dock  and  Smithies  showed  a  man  of 
medium  build,  with  thin  panniculus,  with  marked  cyanosis  over  face  and 
neck;  hands  and  feet  were  moderately  blue;  color  deepened  when  patient 
stood  or  let  his  arms  hang  down.  When  lying  down  face  and  neck  became 
slaty  blue,  the  cyanosis  decreasing  after  several  moments.  Exercise  and 
excitement  increased  the  cyanosis.  Palate  and  tongue  were  deep  purple; 
eyes  prominent,  especially  the  right.  Conjunctivae  suffused,  especially  on 
right.  The  pupils  were  of  moderate  size,  equal  and  active.  The  external 
jugulars  were  prominent,  dilated,  and  filled  from  adove.  There  was  mod- 
erate pulsation  of  the  carotids.  The  thyroid  was  negative;  no  tracheal 
tug.  Over  the  trunk  the  skin  had  a  bluish  cast.  The  thorax  moved  en 
cuirasse;  respirations  were  shallow,  not  increased  when  resting,  but 
rapidly  increasing  on  slight  exertion.  Heart  beat  faintly  seen  in  5  i.  c.  s., 
inside  the  nipple.  Heart  rate  not  increased.  No  arrhythmia.  Palpation  of 
lungs  negative.  Percussion  showed  good  resonance  over  lungs,  low  liver 
dullness,  an  abnormal  area  of  dullness  beneath  the  upp)er  portion  of 
sternum,  and  an  atypically  situated  precordial  outline.  Splenic  dullness 
barely  made  out  to  edge  of  ribs.  Auscultation  of  lungs  showed  diminished 
vesicular  over  entire  right  side  above  fifth  rib;  below  this  inspiration  was 
sharp  and  blowing,  expiration  soft  and  prolonged,  with  few  piping  rales. 
On  the  left  side  there  was  bronchovesicular  breathing  to  the  second  rib, 
with  increased  vesicular  below,  with  more  numerous  rMes.  Spoken  and 
whispered  voice  were  negative. 

Auscultation  of  heart  revealed  faint  sounds  heard  with  difficulty. 
The  first  sound  at  apex  was  soft  and  impure;  the  pulmonic  second  moder- 
ately accentuated.  Over  base  of  heart  sounds  could  barely  be  heard. 


A  CASE  OF  AYERZA'S  DISEASE  1045 

The  radial  pulse  was  slow,  moderately  full,  fuller  on  left  than  on 
right.  Radial  arteries  moderately  sclerotic.  The  blood  pressure  varied  on 
the  two  sides;  on  the  left  systolic  was  156  mm.  Hg,  diastolic  109  mm.; 
on  the  right  the  systolic  was  146,  the  diastolic  98  mm.  (Erianger  apparatus, 
12  cm.  cuff). 

The  abdomen  was  somewhat  distended  in  region  of  umbilicus.  Lower 
border  of  liver  dullness  low.  The  liver  was  felt  with  difficulty  at  the  end 
of  inspiration.  Splenic  dullness  to  edge  of  ribs.  Spleen  was  not  palpable.  No 
palpable  mass  in  abdomen.  Lymph  nodes  not  enlarged. 

Ophthalmologist's  (Dr.  W.  R.  Parker)  examination  of  eyes  showed  a 
moderated  conjunctival  injection;  marked  venous  congestion  of  retina, 
with  edema  of  macular  region.  No  hemorrhages. 

Left  nasal  fossa  was  partly  occluded.  Examination  of  larynx  negative. 

When  presented  in  the  Medical  Clinic,  January  18,  1907,  the  red  blood 
cell  count  was  found  to  be  6,450,000,  white  cells  6500,  and  hemoglobin  100 
per  cent.  The  blood  was  deep  red  in  color,  flowed  slowly.  The  red  cells 
were  normal  in  appearance;  no  nucleated  forms  were  seen,  and  the  differ- 
ential white  count  was  negative.  Urine  contained  a  moderate  amount  of 
albumin,  and  many  small  granular  casts  and  cylindroids.  A  tentative  diag- 
nosis of  " Osier- Vaquez  disease"  was  made  by  Dr.  Dock  at  this  time. 

Later  fluoroscopic  examination  showed  a  vaguely  outlined,  diffuse, 
non-pulsating  shadow  above  the  heart,  especially  dense  about  the  root  of 
the  lungs  and  great  vessels,  extending  up  into  the  neck.  Heart  downwards 
and  inwards.  Diaphragm  low  on  both  sides,  esf)ecially  so  on  right  side. 

A  radiogram  confirmed  the  fluoroscopic  findings,  "a  mass,  almost  as 
dense  as  the  heart,  filling  in  the  mediastinum.  No  definite  lines  of  pulsa- 
tion can  be  seen.  Tumor  apjjears  to  occupy  both  mediastinal  spaces,  lying 
in  close  approximation  to  heart,  lungs,  and  adnexa.  Points  of  greater  or  less 
opacity  can  be  seen  throughout  the  lungs,  the  infiltration  being  more 
marked  on  the  left  than  on  the  right." 

Course  of  Disease.  The  patient  at  first  improved  somewhat  under 
treatment,  was  able  to  go  about  the  hospital,  his  cyanosis,  erythremia, 
and  dyspnea  varying  in  degree  with  conditions.  About  three  months 
after  entrance,  while  walking  in  the  hall,  he  had  a  sudden  sense  of  pressure 
in  upper  thorax,  "felt  as  if  he  were  being  choked,"  could  not  breathe  or 
speak,  fell  to  the  floor  and  became  unconscious.  When  placed  in  bed  was 
cyanotic  and  markedly  dyspneic,  and  complained  of  pains  in  thorax. 
Respiratory  sounds  were  very  weak  with  numerous  piping  rMes;  heart 
sounds  very  weak,  rate  129;  systolic  pressure  106,  diastolic  S5' 

This  attack  was  followed  by  a  period  of  increasingly  frequent  attacks 
of  extreme  cyanosis,  with  more  or  less  pronounced  erythremia,  marked 


1046 


A  CASE  OF  AYERZA'S  DISEASE 


dyspnea,  associated  with  unconsciousness,  headaches,  gastrointestinal 
pain,  and  albuminuria.  He  was  constantly  cyanotic,  but  during  the  two 
years  he  was  in  the  hospital  had  about  seventeen  attacks  of  extreme 
cyanosis  ("black"),  with  extreme  dyspnea,  feeling  of  suffocation,  pre- 
cordial distress  and  palpitation  (angina  hypercyanotica),  these  attacks 
lasting  for  a  few  minutes  or  for  several  hours.  During  the  attacks  the 
heart  rate  was  accelerated,  going  from  60  to  130.  The  peripheral  vessels 
were  injected,  but  there  were  no  p>ositive  venous  pulsations.  During  the 
attacks  there  was  almost  complete  absence  of  breath  sounds,  with  few 
high-pitched  musical  rales.  Heart  sounds  became  very  faint.  The  eye- 
grounds  always  showed  extreme  engorgement  and  edema.  There  was  no 
bleeding,  except  occasionally  from  nose.  Enlargement  of  the  spleen  was 
first  positively  determined  October  21,  1907,  when  it  could  be  palpated 
below  the  edge  of  the  ribs. 

The  erythremia,  which  had  been  noted  on  entrance,  persisted,  varying 
greatly,  usually  in  proportion  to  the  severity  of  the  attacks  of  cyanosis. 
In  over  100  blood  counts  taken  during  the  605  days  in  hospital,  the  red 
blood  cell  count  only  twice  fell  below  6,000,000,  the  lowest  count  being 
5,040,000  on  March  25,  1907,  and  the  highest  9,500,000  on  May  8,  1908. 
The  average  of  these  counts  was  over  8,000,000  per  c.mm.  Blood  taken 
from  different  parts  of  the  body  showed  some  variation  in  the  number  of 
red  cells.  The  hemoglobin  was  always  above  100  per  cent,  frequently  as 
high  as  156  per  cent  (Miescher);  with  prolonged  paroxysms  of  cyanosis 
and  red  blood  cell  counts  of  8,000,000  per  c.mm.  the  average  hemoglobin 
reading  was  132  per  cent.  The  white  cell  count  ran  within  normal  limits, 
6-10,000,  and  the  differential  white  count  showed  little  variation;  at  times 
a  slight  increase  in  eosinophiles  and  lymphocytes,  and  occasionally  a  few 
myelocytes  after  one  of  the  acute  attacks.  Nucleated  reds  were  occasionally 
noted.  With  the  red  cell  count  7,400,000,  specific  gravity  of  blood  was 
estimated  at  1,062;  coagulation  time  shortened;  viscosity  increased. 

The  patient  remained  in  the  hospital  605  days,  being  discharged 
September  12,  1908.  At  the  time  of  discharge  he  was  still  showing  an  in- 
crease in  the  severity  of  his  attacks  of  cyanosis,  dyspnea,  headaches,  visual 
disturbances  (diplopia,  "turning  black"),  gastrointestinal  symptoms  (loss 
of  appetite,  intense  paroxysmal  pains  in  epigastrium  radiating  to  lower 
abdomen,  constipation  alternating  with  diarrhea).  His  albuminuria  had 
increased.  Stools  were  negative.  He  had  no  dysphagia  or  vomiting.  Tem- 
perature was  never  raised.  The  last  radiograms  seemed  to  show  a  gradual 
extension  of  the  mediastinal  mass. 

Dr.  Dock  inclined  to  a  diagnosis  of  Osier- Vaquez  disease  with  albumi- 
nuria and  chronic  pericarditis;  Dr.  Smithies  to  a  diagnosis  of  polycythemia 


A  CASE  OF  AYERZA'S  DISEASE  1047 

with  mediastinal  tumor.  The  case  was  reported  by  the  latter,  as  Case  I, 
in  an  article  on  "Clinical  Aspects  of  Tumors  of  the  Mediastinum."  (2)  In 
this  article,  Dr.  Smithies  summarized  the  case  as  follows:  "The  case  pre- 
sents many  of  the  findings  of  the  condition  of  chronic  cyanosis  with  ery- 
thremia descrih>ed  by  Vaquez,  Osier,  et  al.  The  spleen,  however,  is  not 
enlarged,  and  the  mediastinal  tumor  appears  to  be  a  discoverable  cause 
for  the  symptoms,  which  is  unusual  or  not  yet  reported  for  cases  of  true 
cyanotic  polycythemia,  Vaquez-Osler  malady.  It  is  not  quite  determined 
that  the  two  conditions  do  not  exist,  but  in  view  of  the  rather  marked 
variations  in  the  cyanosis  and  the  red  cell  count,  it  is  probable  that  much 
of  the  polycythemia  is  due  to  extensive  pressure  in  the  thorax  on  the  great 
vessels.  The  changes  in  spleen  and  bone-marrow  might  come  on  later  and 
give  a  characteristic  picture  of  erythremia  vera." 

After  leaving  the  hospital  in  1908,  the  patient  became  a  pop-corn 
peddler  in  Ann  Arbor,  and  was  seen  at  intervals  by  members  of  the  StaflF  of 
Internal  Medicine.  He  was  still  subject  to  attacks  of  cyanosis  and  dyspnea; 
but  was  for  some  time  more  comfortable  than  he  had  been  the  previous 
two  years.  He  was  able  to  work  at  his  pop-corn  business  about  half  the  time. 

On  April  28,  1910,  his  blood  count  was  again  made  in  the  Qinic  of 
Internal  Medicine  (Dr.  A.  W.  Hewlett).  The  red  cell  count  was  7,200,000, 
white  cells  10,500,  and  hemoglobin  120  per  cent.  He  was  first  examined 
by  Dr.  Hewlett  on  the  next  day.  He  found  his  heart  enormously  dilated, 
the  lower  p>ortion  of  the  chest  retracted  and  immobile.  Abdomen  was 
prominent,  but  there  was  no  ascites.  Spleen  was  just  palpable.  Lungs 
showed  signs  of  emphysema,  but  little  bronchitis.  Legs  were  moderately 
edematous.  The  spectroscopic  examination  of  his  fresh  blood,  which  was 
dark  and  thick,  gave  the  characteristic  band  of  oxyhemoglobin.  Urine 
showed  trace  of  albumin  and  few  granular  casts.  He  appeared  at  intervals 
for  examination  and  advice,  his  condition  remaining  about  the  same. 

In  the  Transactions  of  tbe  American  Opbtbalmological  Society,  19 10,  his 
case  was  again  reported,  this  time  from  an  ophthalmological  standpoint, 
by  Drs.  Parker  and  Slocum,  of  the  University  Qinic  of  Ophthalmology. 

By  this  time  the  diagnosis  of  a  mediastinal  tumor  had  been  completely 
abandoned,  and  the  case  was  regarded  as  an  uncomplicated  one  of  "Chronic 
Cyanosis  with  Polycythemia  (Osier- Vaquez  Disease)."  Parker  and  Slocum 
give  in  their  article  (Case  I)  a  detailed  description  of  the  retinal  appear- 
ances of  intense  engorgement  and  edema.  They  noted  the  presence  of  a 
small  venous  aneurysm,  which  later  was  found  to  have  ruptured.  A  second 
retinal  hemorrhage  was  also  seen. 

When  patient  was  seen,  December  2,  1910,  his  cyanosis  was  greatly 
increased;  his  hands  were  black. 


1048  A  CASE  OF  AYERZA'S  DISEASE 

On  January  31,  191 1,  Dr.  Hewlett  found  the  spleen  fairly  easily  pal- 
pable and  "purpuric"  spots  about  his  joints  and  over  his  legs,  some  as 
large  as  a  dime,  and  elevated.  During  the  winter  he  had  a  very  severe  attack, 
and  vomited  black  particles. 

Readmitted  to  the  hospital  on  October  24,  191 1,  his  condition  obliging 
him  to  give  up  work.  At  this  time  he  gave  his  age  as  fifty-two.  His  chief 
complaint  was  still  dyspnea,  weakness,  and  cyanosis.  He  still  denied 
venereal  disease  and  alcoholism.  His  symptoms  were  about  the  same  as 
when  last  seen.  He  had  not  lost  weight;  had  had  no  blood  in  stools  or 
sputum.  Vision  is  blurred  at  times;  and  he  has  headaches  accompanied  by 
dizziness  and  nausea.  Claims  to  sleep  poorly  at  night;  but  is  drowsy  during 
the  day.  Sleeps  between  examinations.  Has  no  thoracic  pain. 

Physical  examination  (Drs.  Hewlett  and  Van  Zwaluwenburg)  showed 
less  cyanosis  than  in  previous  admissions.  Had  firm,  hard  edema  over  thighs 
and  legs,  not  much  over  back;  face  was  puffy.  Conjunctival  vessels  were 
enormously  engorged;  many  venules  were  blue-black.  Veins  of  neck  were  full 
until  patient  was  almost  upright,  when  they  collapsed.  Thorax  moved 
poorly;  there  was  inspiratory  retraction  all  the  way  round  at  level  of  dia- 
phragm. Abdomen  was  full,  flat  above  and  bulging  in  the  flanks.  Abdominal 
breathing  marked.  Percussion  showed  an  enormously  enlarged  heart. 
Liver  was  a  hand's  breadth  below  the  level  of  the  ribs,  reaching  nearly  to 
navel  and  confluent  on  left  with  splenic  dullness.  Lungs  were  nowhere  very 
resonant;  the  lower  borders  moved  slightly,  but  symmetrically.  No  local- 
ized areas  of  diminished  resonance  over  front  or  back.  Tactile  fremitus  was 
negative.  Breath  sounds  all  over  the  lungs  were  feeble,  vesicular,  almost 
inaudible  over  bases  and  back.  Numerous  crackling  rales  were  present 
over  the  upper  portion,  large  dry  ones  below,  somewhat  more  abundant  on 
right.  The  whole  left  upper  portion  more  silent  than  on  right.  No  localized 
voice  changes.  The  first  sound  at  apex  was  dull  and  distant,  almost  replaced 
by  a  systolic  murmur;  second  sound  poorly  heard,  although  easily  felt. 
The  murmur  waned  and  waxed  to  another  maximum  in  the  fifth  i.  c.  s., 
about  2  fingerbreadths  to  left  of  sternum.  It  was  poorly  transmitted  to 
axills,  and  not  heard  in  back.  The  second  sound  in  the  tricuspid  area  was 
relatively  loud.  At  base  both  sounds  were  distant;  valvular  areas  could 
not  be  accurately  localized;  systolic  murmur  from  below  was  only  occasion- 
ally audible  at  base.  No  diastolic  murmur.  The  radial  pulse  was  small, 
soft,  quick,  and  frequent.  Hands  were  cold  and  moist.  The  liver  margin 
was  felt  as  a  firm  semi-elastic  mass  without  a  distinct  edge.  The  spleen  was 
just  palpable  in  the  anterior  axillary  line  in  the  left  hypochondrium.  Other- 
wise belly  was  tympanitic.  No  fluid  wave.  Ophthalmological  examination 
showed  similar  retinal  engorgement  and  edema  as  before,  only  more  marked. 


A  CASE  OF  AYERZA'S  DISEASE  1049 

Erythremia  was  variable  as  before,  7,200,000-8,760,000.  The  white 
cells  ranged  7-10,600;  the  proportionate  count  was  almost  normal,  the 
polynuclears  being  slightly  increased.  No  nucleated  forms  and  no  mye- 
locjrtes  were  found  at  this  time. 

The  patient's  condition  quickly  grew  worse,  increasing  dyspnea  and 
cyanosis,  weakness,  somnolence,  nausea,  "purpura,"  and  finally  bloody 
stools,  blood-streaked  sputum,  delirium,  intense  cyanosis  ("black"),  gen- 
eral collapse,  leading  to  his  death  on  November  14,  191 1. 

Clinical  Diagnosis.  Polyglobulism,  Emphysema.  Cardiac  hypertrophy 
and  dilatation.  Chronic  passive  congestion.  Cardiac  cirrhosis.  Hemorrhage 
from  hemorrhoids.  Nephritis  (?)  (Dr.  Hewlett). 

The  autopsy  was  performed  a  few  hours  after  death. 

Autopsy  Protocol  (Dr.  Warthin).  Male  body,  of  medium  frame,  172 
cm.  long;  abdomen  distended;  umbilicus  everted;  broad  epigastric  angle; 
precordium  prominent.  Skin  of  entire  body  markedly  cyanotic;  where 
least  cyanotic,  on  the  upper  portions  of  body  it  is  yellowish  blue.  Hypo- 
stasis is  extreme,  particularly  on  legs.  Genitals  very  cyanotic  and  slightly 
edematous.  Numerous  angiectatic  warts  over  back,  black  in  color.  Over 
legs  numerous  circumscribed  angiectatic  vessels,  forming  blue-black  spots 
size  of  pin-head  to  dime.  No  hemorrhages  in  skin.  Skin  over  legs  thickened 
and  scaly.  All  superficial  veins  markedly  injected.  Mucous  membranes 
intensely  cyanotic.  Scleree  yellowish.  Musculature  fair.  Fair  amount  of 
panniculus.  Marked  edema  over  legs,  moderate  over  trunk  and  upper 
p)ortion  of  body.  Rigor  mortis  present  throughout.  Palpation  of  abdomen 
negative,  l.iver  and  spleen  could  not  be  felt. 

Head:  SkuII-cap  moderately  thick,  but  almost  as  thin  as  paper  in 
left  temporal  region.  Meningeal  grooves  deeply  eroded,  particularly 
that  of  the  left  middle  meningeal  artery.  Inner  table  shows  marked 
erosion.  In  the  right  temF>oraI  region  there  is  a  sharp,  spine-like  exostosis 
projecting  i  cm.  from  the  inner  table.  Dural  tension  increased.  Dura 
adherent  all  over  convexity,  thickened,  and  very  tough.  Adhesions  between 
dura  and  arachnoid.  Longitudinal  sinus  contains  a  small  red  clot;  the  veins 
opening  into  it  have  markedly  thickened  walls.  Basal  meninges  thickened. 
Arachnoid  over  convexity  thickened,  and  shows  hyaline  patches.  Pial 
vessels  enormously  distended.  Pacchionian  bodies  extremely  small. 
Carotids  and  basal  vessels  show  no  sclerosis.  Cerebrum  intensely  con- 
gested and  edematous.  Ventricles  moderately  dilated.  Chorioid  plexus 
markedly  congested.  Pineal  gland  very  small.  Cerebellum  intensely  con- 
gested and  edematous.  Hypophysis  very  small. 

Spinal  cord  presents  meningeal  thickening,  congestion  and  edema. 

Main  Incision:  Panniculus  very  moist,  light  orange  color.  All  blood 


1050  A  CASE  OF  AYERZA'S  DISEASE 

vessels  engorged  with  dark  fluid  blood.  Muscles  are  light  brownish-red, 
soft,  and  tear  easily.  No  free  gas  in  peritoneal  cavity,  and  only  a  small 
amount  of  clear  fluid  (150  c.c).  Omentum  below  umbilicus,  moderately 
fat,  its  vessels  congested.  Lower  border  of  liver  reaches  to  umbilicus  in 
median  line;  in  right  nipple  line  it  is  a  hand's  breadth  below  edge  of  ribs. 
Spleen  is  large,  its  lower  pole  below  edge  of  ribs.  Stomach  lying  vertically, 
moderately  distended  with  gas.  Curious  sweetish  smell  in  abdominal 
cavity.  Diaphragm  in  lower  border  of  sixth  rib  on  the  right,  in  sixth 
i.  c.  s.  on  the  left. 

Sternum  osteoporotic,  marrow  hyperplastic.  No  free  gas  in  pleural 
cavities.  Small  amount  of  clear  fluid  (100  c.c.)  in  each  cavity.  Old  adhesions 
over  right  apex;  otherwise  pleurae  are  free.  Lungs  nearly  meet  in  upper  por- 
tion of  mediastinum;  their  free  edges  show  extreme  emphysema.  Mediasti- 
nal fat  fairly  abundant,  very  red  in  color.  No  remains  of  thymic  tissue  seen. 

Heart:  Of  enormous  size,  lying  almost  transversely;  the  greater  part 
of  the  right  heart  lies  to  the  right  of  the  median  line,  the  apex  in  sixth 
i.  c.  s.,  half-way  between  nipple  and  anterior  axillary  lines.  Apex  is 
rounded,  blunt,  with  no  point.  Pericardial  sac  greatly  distended;  no 
pericardial  adhesions;  fluid  about  80  c.c,  clear.  All  chambers  of  heart 
greatly  dilated,  particularly  the  right  heart,  the  dilated  right  auricle 
making  up  one-third  of  the  heart  bulk.  Right  border  of  right  auricle 
reaches  to  the  right  parasternal  line.  On  cutting  the  inferior  vena  cava 
there  is  a  gush  of  very  dark  fluid  blood  containing  small  jelly  clots.  Left  and 
right  ventricles  about  equafly  dilated;  both  auricles  extremely  dilated,  the 
right  one  in  a  remarkable  degree;  the  muscle  fibers  of  its  wall  widely 
separated.  The  enlargement  of  the  heart  is  due  chiefly  to  dilatation; 
when  emptied  of  blood  its  measurements  are  18  x  13  x  7.5  cm.,  its 
weight  790  gm.  On  the  table  the  heart  flattens  into  a  soft  round  disk.  The 
subepicardial  fat  is  increased,  orange-red  in  color.  Irregular  tendinous 
spot  over  anterior  waU  of  right  ventricle.  Firm  thrombus  in  right 
auricular  appendage.  Mitral  orifice  admits  five  fingers,  slight  roughening 
and  thickening  of  proximal  edges,  but  no  organic  insufficiency  or  stenosis. 
Aortic  orifice  barely  admits  thumb;  flaps  negative.  Tricuspid  orifice  greatly 
dilated,  admitting  whole  hand;  flaps  negative.  Pulmonary  orifice  admits 
three  fingers,  two  and  a  half  times  as  large  as  the  aortic  opening.  Calcareous 
plaque  in  wall  of  pulmonary  conus.  Pulmonary  artery  enormously  dilated; 
its  wall  markedly  thickened,  and  its  intima  showing  a  condition  of  ad- 
vanced atherosclerosis.  Coronaries  extremely  dilated,  presenting  patches 
of  sclerosis.  Auricular  ventricular  septum  intact;  foramen  ovale  closed; 
no  anomaly.  Aorta  is  of  medium  size;  its  intima  shows  moderate  sclerosis 
rather  linear  in  type,  with  some  early  atheroma. 


— .«^? 


Fig.  I.  Main  Branch  oi  Pul.munak-i  Auiukv, 
5HOWING  Extensive  Atherosclerosis  and 
VIesarteritis. 


Fig.  3.  Media  of  Main  Branch  of  Pul- 
*iONARY  Artery,  Showing  Area  of  Plasma- 
:ell  and  Lymphocyte  Infiltration  of  the 
Media  (Syphilitic  Mesarteritis). 


r ';>>■■ "-«;/. 


^ 


Artery,  at  Edge  of  Sclerotic  Patch. 


I'iG.  4.  Plasma  Cell  Infiltration  about 
One  of  the  Vasa  Vasorum  of  the  Main 
Pulmonary  Artery. 


Fig.    5.     Dilated    and    Sclerotic    Smaller 
Pulmonary  Arterial  Branch. 


Fig.  6.  Am  Containing  Portion  of  Lung, 
WITH  Thick  Alveolar  Walls,  and  Somp 
Emphysematous  Alveoli. 


Fig.  7.  Atelectatic  Fibroid  Area  of 
Lung,  Showing  the  Thickened  Sinusoidal 
Capillaries. 


A  CASE  OF  AYERZA'S  DISEASE  1051 

Lungs:  Right  and  left  lungs  weigh  625  and  675  gm.  respectively. 
Both  are  very  voluminous,  with  markedly  emphysematous  borders. 
Moderate  anthracosis.  Both  show  extreme  congestion  and  edema.  Airless 
areas  alternate  with  emphysematous.  All  the  branches  of  the  pulmonary 
arteries  are  markedly  dilated,  and  present  an  extreme  condition  of 
sclerosis  and  atheroma,  even  to  the  terminal  branches.  Lower  lobes  show 
patches  of  pneumonic  or  hemorrhagic  consolidation.  In  the  larger  main 
branches  of  the  pulmonary  arteries  the  thickened  intima  shows  porcelain- 
like areas,  with  irregular  cracks  and  thinnings  of  the  wall,  as  in  syphilitic 
aortitis.  Pulmonary  veins  enormously  distended;  their  walls  relatively 
thickened.  Bronchial  nodes  pigmented,  much  congested  and  edematous. 

Mouth  and  Neck  Organs:  Mucous  membranes  of  mouth,  pharynx, 
epiglottis,  larynx,  and  trachea  show  extreme  congestion.  Thyroid  is  small, 
with  small  amount  of  colloid.  The  parathyroids  are  of  normal  size,  and 
very  deep  red.  The  cervical  fat  has  the  appearance  of  embryonic  fat. 
Cervical  lymph  nodes  extremely  congested. 

Spleen:  Free,  no  adhesions.  Greatly  enlarged  before  removal;  much 
smaller  after  removal  and  bleeding;  measures  then  13  x  9  x  6.5  cm.,  and 
weighs  330  gm.  Firm,  does  not  flatten  on  pressure.  Capsule  thickened, 
with  small  hyaline  patches.  Cut  surface  shagreened,  deep  bluish-brown- 
red.  Stroma  increased;  follicles  not  easily  seen. 

Adrenals:  Normal  in  size  and  shape.  On  section  show  intense  con- 
gestion. Medulla  of  right  one  in  advanced  post-mortem  change. 

Kidneys:  Left  and  right  measure  13.5  x  8  x  5.25  and  13  x  7.5  x  4.5  cm. 
respectively,  and  weigh  300  and  200  gm.  They  present  similar  appear- 
ances. Fatty  capsules  are  abundant,  reddish  orange,  resembling  fetal 
fat  in  color  and  appearance.  Fibrous  capsules  strip  easily.  Cortical  surface 
smooth,  deep  purple-red,  with  small  areas  of  parenchymatous  degenera- 
tion in  cortex.  Cortex  atrophic.  Cut  surfaces  nearly  uniform  in  color; 
outlines  of  structure  cannot  be  made  out. 

Intestines:  Contain  a  thin,  soup-like,  bile-stained  material.  No  fresh 
blood  seen.  Mucosa  shows  extreme  congestion  and  edema.  Appendix 
surrounded  by  old  adhesions.  Bile  passages  patent.  No  hemorrhoids.  No 
bleeding  in  rectum. 

Stomach:  Contains  a  plum-colored  mucus  containing  some  food 
remains.  No  fresh  blood.  Mucosa  tremendously  congested;  chronic  stasis 
catarrh.  Pylorus  thickened,  firm,  slight  stenosis.  No  erosions  or  ulcers. 

Pancreas:  Large,  firm,  body  ends  abruptly  without  tail.  Color  very 
dark.  On  section  shows  marked  congestion;  lobules  large  with  increase  of 
interlobular  connective  tissue.  Vessels  dilated  and  show  slight  sclerosis. 

Liver:  Much  enlarged,  shows  markings  of  ribs.  After  removal  and  bleed- 


1052  A  CASE  OF  AYERZA'S  DISEASE 

ing  measures  25  x  19  x  8  cm.  and  weighs  2000  gm.  Capsule  shows  some 
thickening,  particularly  around  ligaments.  Lower  border  rather  rounded. 
Consistence  soft.  On  section  bleeds  freely.  Marked  "nutmeg  liver."  Ves- 
sels all  greatly  dilated.  Stroma  increased  in  patches  beneath  cortex.  Gall 
bladder  greatly  distended.  Contains  thin  brownish  fluid. 

Lymph  Nodes:  Mesenteric  and  retroperitoneal  lymph  nodes  extremely 
congested,  edematous,  and  very  soft.  Few  atrophic  hemolymph  nodes, 
brown  in  color. 

Prostate:  Negative,  except  for  intense  congestion. 

Testes:  Marked  congestion  and  edema. 

Bone-marrow:  Hyperplastic  red  marrow  in  sternum  and  ribs.  In  tibiae 
fatty  marrow. 

Microscopic  Findings.  Brain :  Extreme  dilatation  and  congestion  of  all 
vessels,  particularly  of  the  meningeal  and  pial.  Diffuse  thickening  of  the 
inner  meninges.  Chronic  leptomeningitis. 

Cord:  Marked  congestion  of  all  vessels,  particularly  of  the  meningeal. 
Diffuse  thickening  of  the  meninges. 

Heart:  Hypertrophy.  Brown  atrophy.  Fibroid  patches.  Healed  syphi- 
litic myocarditis.  No  active  areas. 

Aorta:  Advanced  atherosclerosis  with  patches  of  active  syphilitic 
mesaortitis. 

Lungs:  Extreme  chronic  passive  congestion  with  numerous  pigmented 
phagocytes,  "brown  induration."  Main  branch  of  pulmonary  artery  shows 
extreme  atherosclerosis  of  the  intima  and  inner  half  of  the  media  with 
active  patches  of  syphilitic  mesarteritis,  and  plasma-cell  infiltrations 
around  some  of  the  vasa  vasorum.  The  intrapulmonary  branches  of  the 
pulmonary  artery  show  extreme  dilatation  with  marked  atherosclerosis  of 
the  intima  and  inner  one-half  to  one-third  of  the  media.  In  the  branches 
of  the  second  and  third  degree  a  few  small  plasma-cell  infiltrations  around 
the  vasa  vasorum  are  found,  but  the  majority  of  these  branches  show  no 
active  syphilitic  lesions.  The  smaller  branches  of  the  pulmonary  vessels 
are  extremely  dilated,  with  thick  hyaline  walls  showing  no  active  process. 
The  alveolar  capillaries  are  greatly  dilated;  have  thickened  hyaline  walls. 
In  some  areas  the  thickened  alveolar  walls  appear  almost  like  that  of  a 
cavernous  angioma.  In  other  areas  the  alveolar  walls  are  atrophic,  hyaline, 
and  the  capillaries  almost  obliterated,  the  alveolar  partitions  extending 
into  the  dilated  infundibula  as  stiff  hyaline  septa.  In  some  j>ortions  of  the 
lung,  the  circulation  is  completely  shut  off  and  the  lung  is  fibroid  and  col- 
lapsed. Hemorrhages  in  all  stages  are  found  everywhere  throughout  the 
lung.  There  is  marked  edema,  and  great  numbers  of  pigmented  phagocytes. 
Emphysematous  areas  are  scattered  through  the  indurated  portions.  The 


A   CASE   OF   AYERZA*S   DISEASE  1053 

hyaline  indurated  portions  of  the  lung  are  particularly  the  seat  of  anthra- 
cotic  deposits.  The  bronchi  and  bronchioles  are  dilated  and  show  catarrhal 
bronchitis.  Small  patches  of  early  broncho-pneumonia  are  also  found,  par- 
ticularly in  the  lower  lobes.  The  pulmonary  veins  are  extremely  dilated, 
and  show  hyaline  thickened  walls  without  atheromatous  changes. 

Thyroid:  Moderate  amount  of  colloid.  Extreme  congestion  of  vessels. 

Tongue:  Numerous  encapsulated  trichinae.  No  reaction  about  these. 

Spleen:  Extreme  dilatation  of  blood  spaces  and  blood  vessels,  many 
portions  resembling  an  angioma  simplex  rather  than  spleen.  The  lymphoid 
tissue  of  the  pulp  is  atrophic.  Follicles  are  of  fair  size,  arterioles  sclerotic. 
The  larger  arteries  show  hyaline  thickening  of  their  walls. 

Adrenals:  Marked  congestion,  particularly  in  the  reticular  zone  and 
medulla.  Extensive  medullary  hemorrhage.  Cortex  shows  extreme  lipoidosis. 
Several  small  plasma-cell  infiltrations  in  the  reticular  zone. 

Kidneys:  Extreme  congestion,  involving  both  arteries  and  veins. 
Marked  hypertrophy  of  glomeruli,  many  being  two  to  three  times  normal 
size,  due  to  increase  in  size  of  capillary  tufts.  Majority  of  Bowman's  cap- 
sules are  thickened,  and  there  is  a  diffuse  increase  of  connective  tissue,  with 
many  scarred  glomeruli,  with  definite  areas  of  chronic  parenchymatous 
nephritis.  Vessels  all  sclerotic.  Slight  cloudy  swelling  of  convoluted  tubules. 

Stomach:  Chronic  catarrhal  gastritis.  Extreme  congestion  of  both 
arteries  and  veins.  In  the  stomach  wall  there  are  numerous  areas  of  plasma- 
cell  infiltration  and  localized  induration,  probably  syphilitic. 

Intestines:  Extreme  congestion  of  arteries  and  veins.  Slight  catarrh. 

Appendix:  Extreme  congestion  of  arteries  and  veins.  Thickening  of 
sub-mucosa. 

Pancreas:  Extreme  congestion  of  arteries  and  veins.  Thickening  of 
vessel  walls.  Fatty  atrophy.  Areas  of  marked  intralobular  interstitial  pan- 
creatitis with  some  active  plasma-cell  infiltrations.  Many  islands  of  Langer- 
hans  are  very  large  and  show  marked  dilatation  of  the  vessels. 

Liver:  Extreme  nutmeg  liver.  Atrophy  and  necrosis  of  cells  of  central 
and  intermediate  zones.  Dilatation  of  all  vessels  with  atrophy  and  slight 
cloudy  swelling  of  liver  cells.  Slight  fatty  degeneration,  particularly  of  the 
central  zones  of  the  lobules.  Capsule  is  thickened,  and  the  lobules  just 
beneath  are  very  atrophic  and  the  periportal  tissue  shows  proliferation, 
small-celled  infiltration  and  new  bile-duct  formation,  the  picture  being 
that  of  a  localized  atrophic  cirrhosis.  These  cirrhotic  changes  a.re  found 
only  beneath  the  capsule. 

Prostate  and  Seminal  Vesicles:  Extreme  dilatation  of  all  vessels  with 
fibroid  hyperplasia.  In  the  seminal  vesicles  are  a  number  of  retention  cysts. 
Spermatic  and  prostatic  plexuses  show  extreme  angiectasia. 


1054  A   CASE  OF   AYERZA'S   DISEASE 

Testes:  Intense  congestion  and  edema.  Diminished  spermatogenesis. 
Increase  of  stroma.  Thickening  of  basement  membrane.  Early  syphilitic 
orchitis  fibrosa. 

Lymph  Nodes:  All  lymph  nodes  show  excessive  dilatation  of  the  ves- 
sels, many  of  the  retroperitoneal  nodes  resembling  angiomas.  Atrophy  of 
lymphoid  tissue  and  increase  of  stroma. 

Semilunar  Ganglia:  Extreme  dilatation  of  vessels,  increase  of  inter- 
stitial tissue  and  pigmentation  of  the  ganglion  cells. 

Bone-marrow:  Tibiae  contain  congested  fatty  marrow,  with  small 
islands  of  red-cell  forming  tissue.  The  sternal  and  rib  marrow  shows 
marked  lymphoid  hyperplasia. 

Adipose  Tissue:  Reversion  to  fetal  typ)e.  Congested  and  edematous. 

Purpuric  Sp)ots:  Telangiectasias. 

Pathological  Diagnosis.  Plethora  vera,  "  Osier- Vaquez  disease"  (ery- 
thremia; chronic  cyanosis  and  splenic  enlargement),  secondary  to  syphilitic 
atherosclerosis  of  pulmonary  arteries;  emphysema  and  brown  induration 
of  lungs;  cardiac  hypertrophy  and  dilatation;  chronic  fibroid  myocarditis; 
syphilitic  aortitis;  chronic  interstitial  gastritis;  atrophy  of  pancreas  with 
chronic  interstitial  pancreatitis;  chronic  syphilitic  orchitis;  chronic  con- 
gestion of  all  organs;  nutmeg  liver;  chronic  splenic  congestion;  hypertrophy 
of  kidneys  with  chronic  parenchymatous  nephritis;  chronic  leptomenin- 
gitis; multiple  telangiectasias  of  skin;  hyperplasia  of  bone-marrow.  Latent 
syphilis;  bronchopneumonia;  old  trichinosis. 

Epicrisis.  This  case  presents  the  complete  symptom  and  patho- 
logic complex  of  the  Osier- Vaquez  disease,  in  the  form  of  a  chronic 
cyanosis,  high  degree  of  erythremia  and  splenic  enlargement,  with 
the  secondary  phenomena  of  dyspnea,  visual  disturbance,  gastro- 
intestinal symptoms,  general  weakness,  congestion,  edema,  etc. 
What  is  of  great  importance  is  the  fact  that  the  autopsy  revealed 
a  condition  to  which  the  Vaquez  symptoms  are  most  probably  sec- 
ondary. It  can  be  very  reasonably  argued  that,  as  the  consequence 
of  a  widespread  lesion  of  the  pulmonary  vessels,  deficient  oxygenation 
of  the  blood-stream  was  produced.  As  a  result  of  the  need  for  oxy- 
genation secondary  emphysema,  hypertrophy  of  the  right  heart  and 
increased  activity  of  the  bone-marrow  developed  as  compensatory 
conditions.  The  cyanosis  is  an  expression  of  the  urgent  need  for 
oxygen;  the  erythremia  is  a  compensation  for  this  need;  while  the 
splenic  enlargement  is  but  a  secondary  result  of  the  plethora  and 
increased  blood  formation  and  destruction.  The  erythremia  itself 


A   CASE   OF   AYERZA'S   DISEASE  1055 

is  brought  about  by  an  increased  activity  (hy|>erplasia)  of  the  bone- 
marrow. 

Further,  the  microscopic  study  of  this  case  shows  also  the  ul- 
timate cause  of  the  whole  complex,  in  that  the  lesion  of  the  pul- 
monary vessels  presents  the  characteristics  of  a  syphilitic  mes- 
arteritis.  This  diagnosis  at  present  rests  upon  the  histologic  features 
alone.  Levaditi  studies  of  this  material  have  just  been  made,  but  no 
spirochaetae  have  as  yet  been  found.  Additional  evidence  of  the  pres- 
ence of  a  syphilitic  infection  is  to  be  found,  however,  in  the  charac- 
teristic myocarditis,  mesaortitis,  pancreatitis,  adrenal  infiltrations, 
chronic  orchitis,  and  possibly  also  the  chronic  leptomeningitis. 
While  the  hospital  records  yield  only  negative  statements  as  to  the 
occurrence  of  a  syphilitic  infection  in  this  patient,  a  letter  from  Dr. 
Frank  Smithies,  now  of  the  Augustana  Hospital,  Chicago,  tells  me 
that  this  patient  was  one  of  the  first  to  receive  a  Wassermann  test 
in  his  laboratory,  in  Ann  Arbor,  and  that  the  reaction  was  positive. 
From  my  own  standpoint,  however,  the  histologic  complex  of  heart, 
vessel,  pancreas,  adrenal  and  testicular  changes  can  mean  but  one 
thing — a  latent  syphilitic  infection.  In  the  meantime,  however,  the 
search  for  the  spirochaetae  will  be  carried  on. 

The  degree  of  arteritis,  sclerosis,  and  atheroma  of  the  pulmonary 
artery  and  its  branches  shown  by  this  case,  is,  I  believe,  unique.  I 
have  been  unable  to  find  in  the  literature  any  description  of  pul- 
monary sclerosis  in  which  the  lesions  appeared  to  be  so  severe  and 
extensive.  In  the  case  repK)rted  by  me,  "Syphilis  of  the  Pulmonary 
Artery:  Syphilitic  Aneurysm  of  the  Left  Upper  Division:  Demon- 
stration of  Spirochaetae  Pallida  in  Wall  of  Artery  and  Aneurysmal 
Sac,"  (3)  the  sclerotic  changes  in  the  left  upper  branch  were  as 
marked,  but  in  the  other  branches  the  degree  of  change  was  much  less. 
The  microscopic  appearances  of  the  pulmonary  vessel  lesions  were 
identical  with  those  in  this  case,  and  the  demonstration  of  the 
spirochaetae  was  accomplished,  both  in  the  artery  wall  and  in  the 
aneurysm. 

The  literature  of  pulmonary  arteriosclerosis  is  rapidly  increasing, 
particularly  in  Spanish-American  reports.  In  tropical  countries 
clinical  cases  of  pulmonary  arteriosclerosis  seem  to  be  more  common, 
and  syphilis  is  regarded  as  the  common  etiological  factor.  In  my 
previous  article  I  collected  4  cases  of  gumma  of  the  pulmonary 


1056  A   CASE   OF   AYERZA'S   DISEASE 

artery,  5  cases  of  gummatous  arteritis,  15  cases  of  pulmonary 
arteriosclerosis  regarded  as  syphilitic  from  the  histologic  appear- 
ances or  the  association  with  other  evidences  of  syphilis,  and  51 
cases  of  aneurysm  of  the  pulmonary  artery  in  which  a  syphilitic 
etiology  was  probable.  (4)  In  one  of  the  reports  (5)  it  is  stated  that 
pulmonary  arteriosclerosis  is  not  a  rare  cause  of  fatal  dropsy  in 
Bengal,  and  Rogers  expresses  his  belief  that  when  it  occurs  between 
the  ages  of  twenty  and  forty  syphilis  is  the  etiological  factor. 

Sanders  (6)  reports  one  case  from  Diirck's  laboratory,  and  collects 
seven  cases  from  the  literature  (Klob,  Crudeli,  Wolfram,  Romberg, 
Monckeberg's  two  cases,  and  Kitamura)  of  a  primary  sclerosis  of 
the  pulmonary  arteries  with  associated  hypertrophy  of  the  right 
heart.  These  were  the  only  reports  of  such  a  complex  that  he  was 
able  to  find.  The  cases  are  incomplete,  both  as  regards  clinical  his- 
tory and  pathological  study,  in  so  far  as  the  question  of  a  syphilitic 
etiology  is  concerned.  It  was  apparently  excluded  or  not  considered. 
Romberg's  case  was  characterized  clinically  by  dyspnea,  cyanosis, 
and  enlargement  oj  liver  and  spleen.  No  mention  of  the  blood  findings. 
Monckeberg's  Case  I  likewise  showed  cyanosis,  with  prominence  of 
eyes,  and  edema.  His  second  case,  a  man  of  fifty-six  years,  presented 
marked  cyanosis,  edema,  dyspnea,  palpitation,  with  enlargement  of 
liver. 

Although  these  cases  are  incomplete,  and  the  condition  of  the 
blood  is  not  stated,  it  seems  probable  that  some  of  them,  at  least, 
fall  into  a  class  showing  the  syndrome  of  chronic  cyanosis,  dyspnea, 
erythremia,  and  pulmonary  sclerosis  recognized  in  Spanish-American 
literature  as  "Ayerza's  Disease"  (Cardiacos  Negros),  from  the  fact 
that  in  a  lecture  given  in  his  clinic  in  1901,  Abel  Ayerza,  Professor 
of  Clinical  Medicine,  National  University  of  Buenos  Aires,  was 
apparently  the  first  to  recognize  the  clinical  entity  of  this  syndrome. 
As  far  as  I  have  been  able  to  discover  the  first  published  use  of  the 
term  "Ayerza's  Disease"  is  in  a  Doctoral  Thesis,  by  Dr.  C.  A. 
Marty,  "La  Tension  Arterial  en  la  Tuberculosis  Pulmonar,"  Buenos 
Aires,  1909,  p.  45,  in  which  he  says  that  there  is  a  special  group  of 
cases  worthy  of  attention  because  of  increased  pulmonary  arterial 
tension  associated  with  hypertrophy  of  the  right  heart,  pulmonary 
arteriosclerosis  and  chronic  cyanosis,  described  eight  years  pre- 
viously by  Ayerza  as  "cardiacos  negros."  The  designation  is  also 


A   CASE  OF   AYERZA*S   DISEASE  1057 

used  by  Escudero  in  his  "Conferencias  Clinicas,"  Buenos  Aires;  and 
by  Garcia  del  Real,  in  "Tratado  de  Patologia  Medica,"  Madrid, 

19 1 7,  IV,  495-530- 

Barlaro  (7)  reports  "A  Case  of  Ayerza's  Disease,"  characterized 
by  extreme  cyanosis,  asthma,  intense  dyspnea,  cardiac  hypertrophy, 
erythremia  (red  cells  6,600,000),  enlargement  oj  liver,  spleen  not  pal- 
pable, Wassermann  +  H — h  +  +  with  pulmonary  arteriosclerosis. 
He  discusses  the  diflFerential  diagnosis  of  Vaquez's  and  Ayerza's  dis- 
eases, and  concludes  that  many  cases  of  Vaquez's  disease  are  really 
cases  of  Ayerza's  disease.  He  so  regards  the  first  case  reported  by 
Vaquez,  the  case  of  Parkes  Weber  and  Watson,  Vaquez  and  Laubrey, 
Saundby  and  Russell,  Osier  (emphysema  without  splenic  enlarge- 
ment), Herringham,  and  others.  Barlaro's  point  seems  to  be  that 
cyanosis  and  bronchial-pulmonary  dyspnea  have  nothing  to  do  with 
a  primary  polycythemia;  if  they  exist  in  association,  the  explanation 
of  the  condition  is  to  be  sought  in  conditions  of  the  pulmonary  artery 
(Ayerza's  disease).  While  his  case  was  undoubtedly  one  of  syphilis, 
Barlaro  is  not  sure  that  all  cases  of  Ayerza's  disease  are  syphilitic 
or  secondary  to  a  parenchymatous  lesion.  He  draws  an  analogy  to 
Raynaud's  disease,  and  thinks  "Raynaud's  disease  in  the  lungs" 
might  account  for  some  of  the  cases  presenting  the  Ayerza  syndrome. 

The  most  complete  description  of  the  Ayerza  syndrome  is  to 
be  found  in  the  monograph  "Esclerosis  Secundaria  de  la  Arteria 
Pulmonar  (Cardiacos  Negros),"  by  F.  C.  Arrillaga,  19 13,  Buenos 
Aires.  Eleven  cases  of  pulmonary  sclerosis  with  extreme  cyanosis, 
dyspnea,  and  erythremia  (in  five  cases  in  which  a  blood  count  was 
made)  are  described,  beginning  with  the  case  seen  by  Ayerza  in 
1 90 1.  The  author  concludes  that  there  can  be  no  doubt  as  to  the 
existence  of  a  morbid  entity  called  "cardiacos  negros,"  and  first 
described  by  Ayerza  in  1901,  characterized  by  cyanosis,  hyper- 
globulism,  dyspnea,  cough  with  expectoration  of  muco-  or  mucopurulent 
sputum,  headache,  angina  hypercyanotica,  hemoptysis,  vertigo,  somno- 
lence, etc.  The  patients  present  first  a  pulmonary  evolution  extending 
over  a  long  period,  then  an  evolution  of  the  cardiacos  negros  state 
lasting  as  a  rule  two  to  five  years.  The  patients  can  die  sleeping, 
without  edema,  after  presenting  a  gallop  rhythm  of  the  right  heart; 
or  death  may  take  place  from  early  myocardial  degeneration  with 
marked  anasarca,  or  from  a  complication,  the  most  common  of 


1058  A   CASE   OF   AYERZA'S   DISEASE 

which  is  broncho-pneumonia.  The  chief  diagnostic  points  in  dis- 
tinguishing from  other  forms  of  cyanosis  are  the  classical  history 
of  antecedent  symptoms  and  the  tempo  of  evolution  of  these,  and 
the  fact  that  the  cyanosis  is  acquired,  and  not  the  final  episode  of  an 
asystolic  condition  as  in  other  forms  of  cyanosis,  but  is  an  initial 
symptom.  The  enormous  hypertrophy  and  dilatation  of  the  right 
heart  is  the  most  important  objective  sign  in  favor  of  a  pulmonary 
rather  than  a  peripheral  obstruction.  Radiography  easily  settles 
the  diagnosis.  The  radiographic  examination  shows  a  low  heart 
shadow,  elongated  and  broadened,  with  rounded,  elevated  apex; 
the  right  border  of  the  right  ventricle  extends  far  to  the  right  of  the 
sternum.  Above  the  left  border  of  the  heart,  at  the  base,  is  a  con- 
vexity due  to  the  left  auricular  appendage,  above  this  the  large 
shadow  of  the  dilated  pulmonary  artery,  and  higher  the  normal 
shadow  of  the  aorta.  Points  of  differential  diagnosis  between  acute 
dilatation  of  the  heart  and  Ayerza's  disease  are  shown  by  the  tempo 
of  evolution  and  the  immense  dilatation  of  the  peripheral  veins  in 
the  former  condition,  while  the  "cardiacos  negros"  have  "almost 
no  veins."  As  to  the  etiology,  the  lesions  in  the  pulmonary  vessels 
may  be  secondary  to  chronic  pulmonary  disease,  bronchitis,  tuber- 
culosis, pleural  adhesions,  or  any  condition  producing  a  final  em- 
physema; or  it  may  be  the  result  of  slow  infections,  as  syphilis,  or 
malaria,  or  the  result  of  intoxications. 

Summary.  I  am  of  the  opinion  that  the  clinical  and  pathological 
study  of  the  case  given  in  this  paper  separates  it  from  the  Vaquez 
group  of  erythremias  into  the  class  that  Ayerza  first  pointed  out  as 
a  distinct  clinical  and  morbid  syndrome.  The  long  pulmonary- 
evolution  of  the  symptoms  in  the  form  of  asthma  and  dyspnea,  the 
later  slow  evolution  of  the  cyanosis,  erythremia,  and  secondary 
symptoms  are  characteristic  of  the  Ayerza  cases.  The  autopsy 
revealed  a  unique  picture  of  extreme  atherosclerosis  of  the  pul- 
monary arteries,  and  the  microscopic  study  shows  the  picture  of  a 
latent  syphilis.  The  radiograms  should  have  revealed  the  condition 
at  first,  had  anyone  at  that  time  heard  of  Ayerza's  disease  and  had 
thereby  been  enabled  to  make  a  correct  interpretation  of  the  radio- 
graphic findings.  The  original  radiograms  have  disappeared,  but 
a  pencil  sketch  which  remains  of  the  shadows  seen  and  interpreted 
as  a  mediastinal  tumor  is  almost  a  duplicate  of  the  radiographic 


A   CASE   OF  AYERZA'S   DISEASE  1059 

illustration.  Fig.  IX,  in  Arrillaga's  monograph,  in  which  the  shadow 
of  the  dilated  pulmonary  artery  is  very  well  shown. 

The  erythremia  in  Ayerza's  disease  is  beyond  question  a  sec- 
ondary compensatory  process,  an  increased  functional  activity  of 
the  bone-marrow  to  meet  the  deficiency  in  oxygen  supply  due  to  the 
obstructed  pulmonary  circulation.  It  is  most  probable  that  this  is 
the  case  in  all  forms  of  Vaquez's  disease;  certainly  in  all  of  those  in 
which  there  is  cyanosis  and  dyspnea.  Neither  one  of  these  symptoms 
belongs  to  a  primary  erythremia;  and  when  they  are  present  it  is 
certain  that  the  erythremia  is  secondary.  Likewise,  the  splenic 
enlargement  is  not  an  essential  feature  of  the  syndrome;  it  is  also 
secondary,  and  its  appearance  in  the  disease  may  be  early  or  late, 
according  to  varying  conditions  of  congestion  and  increased  splenic 
function.  Cases  of  congenital  defects  of  the  septum  of  the  heart 
have  been  reported,  showing  the  highest  degree  of  erythremia, 
cyanosis,  and  marrow  hyperplasia — the  essential  features  of  the 
Osier- Vaquez  disease;  and  the  same  complex  may  arise  as  the  result 
of  other  conditions  leading  to  a  chronic  oxygen  deficiency. 

The  Osier- Vaquez  complex  of  cyanosis,  erythremia,  and  splenic 
enlargement  is  a  syndrome  having  a  varied  pathology  and  etiology, 
and  is  not  a  specific  morbid  entity.  From  Vaquez's  disease  there  can 
be  separated  a  group  of  cases  showing  the  Vaquez  syndrome  asso- 
ciated with  atherosclerosis  of  the  pulmonary  arteries,  and  possessing 
distinctive  clinical  and  diagnostic  features.  To  this  group  of  cases 
the  designation  "Ayerza's  disease,"  or,  preferably,  "Ayerza's  syn- 
drome," should  be  applied.  The  case  described  in  this  paper  is, 
therefore,  the  first  one  of  this  type  to  be  recognized  in  this  country, 
and  to  be  reported  in  English. 

BIBLIOGRAPHY 

1.  Arcb.  Int.  Med.f  19 12,  X,  597. 

2.  J.  Am.  M.  Ass.t  1908,  LI,  897. 

3.  Am.  J.  Sypb.,  I,  19 17. 

4.  For  literature,  see  article  cited  above. 

5.  Rogers,  1909. 

6.  Arcb.  Int.  Med.  1909,  III,  257. 

7.  Rev.  Assoc.  Argent.,  1917,  XXVI,  121 


DESCRIPTION  OF  A  MINUTE  SARCOMA,  NECESSI- 
TATING REMOVAL  OF  THE  EYEBALL,  WITH 
HISTOLOGICAL  FINDINGS 

By  John  E.  Weeks,  M.D.,  New  York 

THE  following  case  is  reported  because  of  several  unusual 
features,  among  which  are:  (a)  The  growth  is  the  smallest 
of  which  I  can  find  a  report  in  literature,  for  the  presence  of 
which  an  eyeball  has  been  removed;  (b)  an  opportunity  to  observe 
the  progress  of  the  growth  from  the  beginning  of  its  development; 
(c)  the  location  of  the  growth;  (d)  the  site  of  the  development,  and 
(e)  the  participation  of  the  cells  of  the  pigment  layers  of  the  retina 
in  the  pigmentation  of  the  growth. 

October  15,  191 0,  Mr.  F.  W.  C,  age  thirty-one,  consulted  me  regarding 
the  condition  of  his  left  eye.  The  patient  first  noticed  slight  blurring  of 
the  vision  of  the  left  eye,  accompanied  a  few  weeks  later  by  flashes  of 
light,  two  months  before  consulting  me.  No  pain  had  been  experienced. 

Status  praesens:  Right  eye  normal. 

Left  eye,  anterior  segment  of  globe  normal.  Vision  with  a  correcting 
lens  equals  20/100  +,  slightly  eccentric,  images  distorted.  On  examining 
the  fundus,  a  condition  was  observed  at  the  macula,  roughly  represented 
in  Fig.  I,  B.  There  was  apparently  a  detachment  of  the  retina  over  the 
entire  area,  without  any  exudation  in  the  retina  itself.  The  outer  zone 
was  pale,  but  in  the  center  there  was  a  brownish  area,  indicating  the 
presence  of  a  pigmented  slightly  raised  mass.  In  size  the  affected  area  was 
slightly  smaller  than  the  optic  disk  in  all  diameters  (approximately  i 
millimeter  in  the  lateral  and  in  the  vertical  diameters).  The  elevation  of 
the  mass  was  2/3  millimeter.  The  field  of  vision  was  normal  in  extent,  but 
there  was  a  very  small  absolute  central  scotoma,  and  a  pericentral  rela- 
tive scotoma,  as  represented  in  Fig.  2. 

A  tentative  diagnosis  of  neoplasm  was  made,  and  the  patient  was 
advised  to  present  himself  from  time  to  time.  In  addition  to  recording 
the  field  of  vision,  careful  drawings  were  made,  particularly  in  reference 
to  the  relation  of  the  blood  vessels  to  the  various  parts  of  the  growth, 
for  the  purpose  of  determining  increase  or  decrease  in  the  size  of  the  mass. 

1060 


DESCRIPTION  OF  A  MINUTE  SARCOMA 


1061 


Oct.1s.19u}. 


Since  an  exudation  or  growth  in  the  chorioid  or  retina  may  be  due  to  a 
number  of  causes,  examination  and  tests  were  made  to  eliminate  tuber- 
culosis, syphilis,  accessory  sinus  disease,  etc.,  and  mercury  and  potassium 
iodide  were  administered  for  a  number  of  months.  These  investigations 
did  not  disclose  any  tangible  condition  that  could  stand  in  a  causative 
relation. 

October  28th  the  elevation  of  the  mass  is  1.5  mm. 

November  25th,  a  small  hemorrhage  has  apjjeared  within  the  lower 
boundary  of  the  mass. 

February  14,  191 1,  the  growth  has  enlarged  appreciably  (see  Fig.  i,  D,) 
elevation  2  mm.  There  are  a 
number  of  small  hemorrhages 
along  the  lower  margin,  ap- 
parently  beneath  as  well  as  in 
the  retina.  As  seen  with  the 
ophthalmoscope,  the  size  of 
the  mass  as  compared  with 
the  size  of  the  optic  disk  was 
greater  in  the  vertical  and 
about  the  same  in  the  horizon- 
tal diameter  equal  to  2  mm.  by 
1.5  mm.  Since  the  presence  of  a 
neoplasm  could  not  be  doubted, 
enucleation  was  advised.  On 
consent  of  the  patient  this  was 
done  without  farther  delay. 

After  removing  the  eyeball 
it  was  transilluminated  and  a 

slight  shadow  was  demonstrated  when  the  source  of  illumination  passed 
the  posterior  pole  of  the  globe.  On  opening  the  globe,  which  was  done  by 
a  horizontal  anteroposterior  section  in  the  equatorial  meridian,  after  hard- 
ening in  formalin,  a  small  brownish  mass,  apparently  of  the  chorioid,  was 
found  at,  or  very  slightly  above,  the  macula.  The  retina  was  detached  and 
slightly  raised  at  this  point.  On  measuring,  the  brownish  mass  was  found 
to  be  1.5  mm.  in  the  horizontal,  i  mm.  in  the  vertical  diameters  and  ap- 
proximately 0.5  mm.  thick,  of  a  very  dark  brown  color  (almost  black). 
(See  Fig.  3.) 

The  tissue  was  hardened  in  formation,  then  embedded  in  celloidin  and 
several  sections  made  of  the  growth. 

The  mass  was  found  to  be  composed  for  the  most  part  of  spindle- 
shaped  cells,  some  of  which  are  pigmented,  and  elongated,  irregularly  shaped 


i>bim  1911. 


Fig.  I.  A  and  C,  Optic  Disk;  B,  Growth  when 
First  Observed;  D,  Growth  as  Observed  before 
Enucleation. 


io62        DESCRIPTION  OF  A  MINUTE  SARCOMA 

chromophores  apparently  derived  from  the  retinal  pigmented  epithelial 
cells.  These  cells  have  multiplied,  and  some  have  wandered  into  or  have 
been  carried  away  from  the  pigmented  layer  of  the  retina  by  the  cells  of 
the  tumor  in  the  progress  of  growth.  (See  Fig.  4.)  The  blood  vessels  in  the 
tumor  mass  are  not  numerous,  but  there  are  some  to  be  seen  mostly 


situated  near  the  base  of  the  mass.  These  present  the  characteristics  of 
blood  vessels  in  sarcoma  tissue.  A  remarkable  feature  of  this  tumor  is 
that  it  is  located  almost  wholly  on  the  inner  asf)ect  of  the  pigment  layer 
of  the  retina.  At  one  part,  at  the  margin  of  the  tumor  mass,  there  appears 
to  be  a  break  in  the  continuity  of  the  pigment  layer  of  the  retina  and  the 
lamina  vitrea,  and  the  cells  of  the  choric  capillaris  and  underlying  tissue 
of  the  chorioid  appear  to  mingle  with  the  cells  of  the  tumor  mass.  However, 
I  cannot  discover  any  cells  that  are  beyond  doubt  sarcoma  cells  in  the 


DESCRIPTION  OF  A  MINUTE  SARCOMA 


1063 


tissues  of  the  chorioid  posterior  to  the  chorio-capillaris,  and  the  presence 
of  sarcoma  cells  in  the  chorio-capillaris  is  not  absolutely  certain.  This 
growth,  which  must  be  classed  with  the  sarcomata,  consists  of  cells  of  the 
connective-tissue  type,  mingled  with  chromophores  derived  from  epithelial 
cells.  The  connective-tissue  type  of  cells  were,  in  all  probability,  developed 
from  the  chorio-capillaris  of  the  chorioid.  The  site  of  the  sarcoma  is  unique 
so  far  as  I  have  been  able  to  discover  in  the  literature. 


Fig.  3.  I,  Section  of  Short  Ciliary  Vessels;  2,  Sclera;  3,  Chorioid;  4,  Choriocapillaris; 

5,  Tumor. 

In  regard  to  the  origin  of  sarcoma  of  the  chorioid,  Fuchs  and 
many  others  hold  that  all  sarcomata  originate  in  the  deeper  layers 
of  the  chorioid.  However,  there  is  a  difference  of  opinion  regarding 
the  place  of  origin  of  the  so-called  leuco-sarcomata  of  the  chorioid 
(as  a  matter  of  fact  leuco-sarcoma  of  the  chorioid  invariably  presents 
some  pigment  in  some  part  of  the  growth.  Half  of  the  same  neoplasm 
may  be  deeply  pigmented  and  half  almost  entirely  free  from  pig- 
ment). In  the  opinion  of  H.  Knapp,  (i)  Briere,  (2)  and  Schieck  (3) 
these  tumors  spring  from  the  chorio-capillaris.  Leber  (4)  has  raised 
the  question  as  to  whether  the  pigment  epithelium  of  the  retina 
does  not  enter  into  the  formation  of  the  pigment  in  melanosarcomata 
of  the  chorioid,  and  concludes  as  follows: 


io64        DESCRIPTION  OF  A  MINUTE  SARCOMA 

1.  "A  portion  of  the  pigmented  cells  of  melanosarcoma  of  the  chorioid 
is  derived  from  the  pigment  cells  of  the  retina  .  .  . 

2.  "The  pigment  of  these  cells  is  derived  from  the  pigment  of  the 
blood,  and  its  presence  in  the  cell  is  due  to  a  phagocytic  action  of  the 
cells  on  the  red  blood  corpuscles.  The  pigment  of  the  branching  pigmented 
ceils  of  the  chorioid  is  not  of  hematogenous  origin. " 

The  opinion  that  the  retinal  pigment  cells  take  part  in  many 
cases  in  the  development  of  the  pigmented  cells  in  sarcomata  is 
held  by  E.  V.  Hiipfel,  (5)  Leber,  Lagrange,  (6)  Schieck,  and  others. 
Schieck,  however,  is  positive  that  this  does  not  occur  so  long  as  the 
lamina  vitrea  is  intact. 

Under  the  title  "Smallest  Sarcoma  of  the  Chorioid,"  Fuchs  (7) 
reports  three  cases  occurring  in  the  eyes  that  were  removed.  One 
post-mortem,  the  man  having  died  with  symptoms  of  tumor  of  the 
brain;  the  second  an  eye  excised  for  glaucoma,  the  third  an  eye 
excised  for  suppuration  of  the  cornea  after  injury.  On  microscopical 
examination  the  growths  were  discovered  and  diagnosed.  The  di- 
mensions were  first  0.7  by  0.8  by  0.15  mm.;  second  1.25  by  1.5  by 
.009  mm.;  third  2.25  by  i.  by  0.25  mm.  All  originated  in  the  deeper 
layer  of  the  chorioid. 

BIBLIOGRAPHY 

1.  "On  Intra-ocular  Tumors,"  Wood,  N.  Y.,  1868,  225. 

2.  "Etud.  din.  et  anat.  sur  le  Sarcome  de  la  chorioide,"  Th^se  de  Paris, 

1873. 

3.  Graeje's  Arcb.,  XLV,  No.  2,  and  XLVIII,  No.  2. 

4.  Graeje's  Arcb.  of  Opbtb.,  XLIV,  683. 

5.  Arcb.  f.  Opbtb.,  XL,  Nos.  i  and  4. 

6.  "Nemeurs  de  L.  CEil"  Paris,  1901. 

7.  Tr,  Am.  Opbtb.  Soc,  XII,  787,  191 1. 


Fig.  4.  Section  of  Tumor,  Choroid  and  Underlying  Sclera. 


INTOXICATION  OF  INTESTINAL  OBSTRUCTION 

TOXIC   PROTEOSES   NOT  DESTROYED   IN   INTESTINAL  TRACT  AND 
NOT   FORMED   IN   COLON    LOOPS 

By  G.  H.  Whipple,  M.D.,  San  Francisco 

(From  the  George  Williams  Hooper  Foundation  for  Medical  Research  University  of 
California  Medical  School,  San  Francisco) 

MUCH  has  been  written  about  the  interesting  type  of  in- 
toxication which  develops  with  an  intestinal  obstruction. 
The  fact  that  many  explanations  have  been  championed 
by  diflferent  investigators  and  clinical  observers  is  sufficient  proof 
that  convincing  evidence  is  not  at  hand  to  explain  all  the  observed 
reactions.  We  wish  to  point  out  several  observations  and  add 
other  experiments  which  bear  on  this  subject.  We  believe  that 
some  of  these  facts  have  been  overlooked  by  some  of  the  recent 
investigators  and  that  a  proper  grasp  of  these  data  will  clear  the 
field  of  many  confusing  and  apparently  contradictory  theories. 

It  is  now  admitted  by  practically  all  investigators  in  this  field 
that  a  poison  is  formed  in  the  body  and  is  responsible  for  the  in- 
toxication which  develops.  Where  this  poison  develops,  what  its 
nature  may  be,  and  how  it  is  formed  are  questions  open  to  debate 
and  have  been  discussed  with  much  earnestness  and  even  polemical 
vigor  by  the  many  workers  who  are  seeking  the  solution  of  this 
problem.  That  this  intoxication  is  purely  "non-specific"  gives  it 
an  added  interest  to  many  workers,  and  makes  it  probable  that 
information  gained  concerning  this  intoxication  may  have  value 
in  the  proper  understanding  of  the  "non-specific"  fraction  of  intox- 
ications associated  with  bacterial  infection. 

One  most  important  point  has  been  lost  sight  of  and  needs 
constant  emphasis — Nothing  produced  within  the  lumen  of  the 
intestinal  tract  can  be  directly  concerned  in  the  intoxication  of  in- 
testinal obstruction,  because  the  intestinal  epithelium  is  impervious 
to  all  toxic  substances  which  can  be  demonstrated  in  any  amount 
in  the  material  accumulating  in  the  obstructed  intestine.     Material 

1065 


io66    INTOXICATION  OF  INTESTINAL  OBSTRUCTION 

obtained  from  the  obstructed  intestine  can  be  fed  in  unlimited 
quantities  or  injected  into  the  normal  duodenum  or  obstructed 
intestine,  or  into  closed  loops  of  the  intestine  without  causing  the 
slightest  degree  of  intoxication.  These  facts  have  been  demonstrated 
beyond  any  doubt  in  published  experiments  (i,  2)  and  the  data 
given  below  add  confirmatory  evidence.  Therefore  we  need  not  con- 
cern ourselves  with  hypothetical  toxins  which  may  be  produced 
in  the  lumen  of  the  obstructed  intestine  by  bacterial  growth  or  by 
ferment  cleavage  of  protein  substances.  There  is  no  evidence  that 
any  such  toxins  are  formed  under  the  condition  of  intestinal  obstruc- 
tion, but  if  they  are  formed  they  cannot  be  concerned  in  the  general 
intoxication,  because  these  substances  cannot  be  taken  up  by  the 
intact  intestinal  mucosa. 

We  believe  that  the  epithelium  of  the  mucous  membrane  of 
the  small  intestine  under  obstruction  conditions  is  able  to  form 
a  toxic  substance  or  substances,  and  that  this  poison  can  be  formed 
only  by  the  intestinal  epithelium.  Unusual  development  of  intestinal 
bacteria  may  act  as  a  stimulant,  but  the  essential  thing  is  that  the 
toxic  substance-  must  be  Jormed  in  the  mucous  membrane.  As  the 
poison  is  being  formed  in  the  mucosa  of  the  small  intestine  a  part 
of  it  is  taken  up  by  the  blood  stream  and  causes  the  characteristic 
clinical  reaction,  a  part  is  not  taken  up,  but  is  excreted  into  the 
lumen  of  the  gut,  and  once  in  the  intestinal  lumen  the  poison  is 
inert  in  so  far  as  the  host  is  concerned.  This  portion  of  the  poison 
may  be  obtained  from  the  material  in  the  lumen  of  the  obstructed 
intestine.  It  is  to  be  kept  in  mind  that  this  poison  is  not  found  in 
the  normal  intestine. 

The  substance  or  substances  which  we  have  isolated  from  obstruc- 
tion material  have  been  described  in  other  communications  (3)  (4). 
It  is  sufficient  to  say  that  the  evidence  points  to  the  proteose  group 
of  substances,  and  we  shall  use  the  term  "proteose"  with  proper 
mental  reservation  to  indicate  the  possibility  of  other  large  molec- 
ular substances  being  present  in  the  "proteose  mixture." 

EXPERIMENTAL   OBSERVATIONS 

Closed  Loop  of  Colon.  Duration  Ten  Months.  Dog  18-8.  Collie.  Healthy 
Female.  Weight  25  pounds.  July  19,  191 7.  A  closed  loop  of  colon  done  in 
the  usual  way  by  Dr.  Wooisey  and  Dr.  Kerr.  The  loop  included  about 


INTOXICATION  OF  INTESTINAL  OBSTRUCTION     1067 

3  inches  of  the  ileum  and  all  of  the  colon  up  to  about  5  inches  from  the 
anus.  The  ends  were  cut  across  and  inverted.  A  lateral  anastomosis 
was  made  between  the  ileum  and  rectum  to  re-establish  the  intestinal 
tract. 

July  23d  to  31st.  Uninterrupted  convalescence.  Weight  25  pounds. 

Oct.  3d.  Dog  is  normal  and  lively.  Weight  29.5  pounds.  Isolated  in 
metabolism  cage  without  food. 

Oct.  4th.  A  small  amount  of  fecal  material  removed  from  cage  and 
discarded. 

3  P.M.  A  solution  of  toxic  proteose,  200  c.c.^  given  by  stomach  tube. 
Obtained  from  autopsy  17-60,  described  below. 

Oct.  5th.  ID  A.M.  Dog  normal  in  every  respect.  No  feces. 

Again  given  200  ex.  0/  a  solution  of  toxic  proteose.  Autopsy  17-60. 
There  is  no  clinical  reaction  following  either  administration  of  proteose. 

2  P.M.  Soft  yellow  semi-fluid  feces  passed  and  immediately  collected 
from  cage.  Weight  50  grams. 

Fecal  material  dissolved  in  water  (about  100  c.c),  separated  by 
centrifuge  and  the  supernatant  fluid  precipitated  by  five  volumes  of  95 
per  cent  alcohol.  This  alcoholic  precipitate  dissolved  in  distifled  water, 
slightly  acidified  and  boiled,  then  filtered  to  remove  a  small  amount  of 
precipitate.  This  neutralized  watery  extract  of  the  alcoholic  precipitate 
was  shown  to  contain  much  toxic  proteose-Iike  material  tested  on  Dog 
18-57.  This  dog  was  severely  but  not  fatally  intoxicated.  See  below. 

Oct.  6th,  10  A.M.  Soft  semi-fluid  yellow  feces,  30-40  grams  in  weight, 
collected  carefully  and  extracted  for  proteose  exactly  as  described  for 
preceding  day.  This  material  tested  on  Dog  18-58  gave  a  lethal  and  typical 
intoxication,  fatal  within  five  hours.  The  autopsy  findings  were  typical 
of  acute  intoxication  following  the  intravenous  injection  of  proteose  ma- 
terial obtained  from  cases  of  intestinal  obstruction. 

12  M.  Dog  given  200  c.c.  milk  by  stomach  tube.  Dog  normal  in  all 
respects. 

Oct.  7th.  No  feces  passed. 

Oct.  8th.  10  A.M.  Soft  semi-fluid  yellow  feces,  50  grams  in  weight, 
collected  as  usual  and  extracted  for  proteose-Iike  material  exactly  as  de- 
scribed above.  This  extract  was  tested  upon  Dog  18-55  and  was  shown  to 
contain  no  toxic  material  whatsoever.  (Control  period.) 

Mar.  II,  1918.  Dog  18-8  in  normal  condition.  Weight  30.8  pounds. 

May  15th.  Dog  is  not  in  good  condition  and  shows  evidence  of  definite 
intoxication.  Abdomen  is  prominent.  Weight  32  pounds. 

May  17th.  Dog  is  very  sick.  Abdomen  distended.  Vomiting.  Ether 
anesthesia  and  sacrifice. 


io68    INTOXICATION  OF  INTESTINAL  OBSTRUCTION 

Autopsy  performed  at  once.  Thorax,  heart,  and  lungs  normal.  Peri- 
toneal cavity  contains  3000  c.c.  turbid  straw-colored  fluid  with  a  sedi- 
ment of  granular  material,  the  granules  of  fibrin  measuring  2  to  3  mm.  in 
diameter.  Serous  surfaces  are  injected  and  swollen,  the  omentum  particu- 
larly. Stomach  contracted  and  normal;  small  intestines  collapsed  and 
normal  throughout;  the  anastomosis  between  the  ileum  and  colon  is 
imbedded  in  a  mass  of  dense  adhesions  which  contain  some  pus  pockets. 
This  long  latent  period  is  of  some  surgical  interest.  These  foci  of  infection 
undoubtedly  explain  the  general  peritonitis.  Spleen  is  somewhat  enlarged 
and  mottled.  Liver  pale  and  yellow  and  contains  two  superficial  small 
pus  pockets  just  beneath  the  capsule  anteriorly.  This  is  the  result  of  an 
extension  of  the  inflammatory  process  from  the  peritoneum  into  the  paren- 
chyma. Pancreas  and  kidneys  are  normal. 

Loop  of  Colon.  Its  walls  are  definitely  hypertrophied,  particularly  in 
the  short  stump  of  the  ileum.  There  are  very  few  adhesions  over  the 
serous  surfaces.  The  mesentery  is  thick  and  tendinous.  Mucous  membrane 
is  normal,  perhaps  a  little  thickened.  The  inverted  ends  are  clean  and  the 
most  careful  examination  shows  no  ulcers  anywhere.  The  ileum  measures 
3  inches  in  length  and  contains  only  traces  of  yellowish  fecal-Iike  material. 
A  large  sausage-like  mass  of  material  was  packed  into  the  lower  colon. 
This  material  is  putty-like  in  consistency  and  of  a  dark  slaty  color.  It 
separates  very  easily  and  cleanly  from  the  mucous  membrane.  It  is  homo- 
geneous throughout. 

Microscopical  sections  in  general  are  negative.  Liver  shows  a  little  cen- 
tral fatty  degeneration.  Sections  from  the  stomach,  intestines  and  various 
parts  of  the  closed  loop  show  normal  epithelium  everywhere. 

Material  Jrom  closed  loop  weighs  126  grams.  It  was  ground  up  in  about 
250  c.c.  of  distilled  water,  sand  being  added  in  the  mortar.  It  was  reduced 
to  a  thin  soupy  fluid  and  then  shaken  Jor  hours  in  the  shaking-machine. 
All  particles  were  thrown  down  by  the  centrifuge,  giving  a  supernatant 
fluid  of  opalescent  gray  appearance.  This  was  precipitated  with  five  vol- 
umes of  95  per  cent  alcohol.  After  standing  for  two  days  the  alcoholic 
precipitate  was  dissolved  in  water  (700  c.c),  made  slightly  acid  to  litmus 
with  acetic  acid,  brought  to  a  boil  and  filtered.  The  filtrate  was  concen- 
trated over  a  water-bath  after  neutralization  to  100  c.c.  All  of  this  material 
was  given  intravenously  to  Dog  19-19.  There  were  no  evidences  of  intoxi- 
cation. See  below. 

Toxic  Proteose  Jrom  Case  of  Human  Obstruction,  Autopsy  17-60. 
Young  adult  male;  operation  upon  lower  ileum.  Shortly  after  this  opera- 
tion evidences  of  intestinal  obstruction  developed  with  very  rapid  intoxi- 
cation and  death.  Autopsy  was  performed  within  two  to  three  hours 


INTOXICATION  OF  INTESTINAL  OBSTRUCTION     1069 

post-mortem.  A  kink  in  the  ileum  was  found  just  above  the  enterostomy 
wound. 

Intestinal  fluid  was  obtained  in  large  amounts  from  the  distended 
ileum.  This  material  had  the  usual  appearance  and  odor  characteristic  of 
such  material.  It  was  cleared  by  the  centrifuge  and  the  watery  broth- 
like fluid  material  was  poured  into  five  volumes  of  95  per  cent  alcohol. 
After  several  days  the  alcoholic  precipitate  was  taken  up  in  distilled  water, 
acidified  with  acetic  acid,  brought  to  a  boil,  and  filtered.  This  clear  amber 
filtrate  was  neutralized  and  tested  out  on  a  normal  dog,  18-43.  Weight 
27  pounds.  Ten  c.c.  per  pound  body  weight  given  intravenously  gave  a 
very  severe,  almost  fatal,  intoxication  with  repeated  vomiting,  bloody 
diarrhea,  and  prostration.  This  material  (4000  c.c.  in  all)  was  then  con- 
centrated to  2000  c.c,  autoclaved,  and  preserved.  It  is  obvious  that  5  c.c. 
per  pound  body  weight  should  approximate  a  lethal  dose.  This  human 
material,  containing  much  of  the  characteristic  poison,  was  given  by 
stomach  tube  in  considerable  doses  to  the  dog  18-8,  used  in  the  first  experi- 
ment. 

Proteose  Recovered  from  Feces  after  Administration  6y  Moutb.  Dog 
18-57.  Fox-terrier,  adult  female.  Weight  24.3  pounds. 

Oct.  29th,  12  M.  Ether  anesthesia  and  intravenous  injection  of 
proteose  extract  obtained  from  Dog  18-8;  Jecal  material  of  Oct.  $tb.  200  c.c. 
total  amount  of  deep  amber-colored  fluid.  This  injection  caused  little 
depressant  eff'ect  on  blood  pressure. 

12:40  P.M. — ^Temperature  38.3.  Passed  solid  feces. 
2:00        — ^Temperature  38.0. 

2:30        — ^Temperature  38.4.  Diarrhea  and  vomitus. 
3:20        — Temperature  38.8.  Dog  very  sick.  Bile-stained  vomitus. 
3  ".50         — ^Temperature  39.  i .  Continuous  vomiting  and  diarrhea. 
4:45         — Temperature  39.2.  Vomiting  continuous. 
5:30        — ^Temperature  39.1.  Clinical  improvement. 

Oct.  30th:  Dog  appears  well. 

This  experiment  shows  that  toxic  proteose  material  from  a  case  of 
intestinal  obstruction,  fed  to  a  dog  with  excluded  large  intestine,  may  be 
recovered  unchanged  from  the  feces.  There  is  no  resultant  intoxication 
from  feeding  this  poison.  The  toxic  proteose  is  able  to  resist  the  action 
of  the  digestive  enzymes  of  the  stomach  and  small  intestine  for  a  period 
of  forty-eight  hours  or  longer.  We  have  reported  (5)  experiments  to  show 
that  this  toxic  substance  is  able  to  resist  long  periods  of  digestion  in 
vitro. 

Proteose  Isolated  from  Feces  after  Administration  by  Moutb.  Dog  18-58. 
Fox-terrier,  small  adult  male.  Weight  12.8  pounds. 


1070    INTOXICATION  OF  INTESTINAL  OBSTRUCTION 

Oct.  29th,  12  M.  Ether  anesthesia  and  intravenous  injection  of  pro- 
teose extract  obtained  Jrom  Dog  18-8.  Fecal  material  oj  Oct.  6tb.  150  c.c.  total 
amount  of  amber-colored  opalescent  fluid. 

12:40  P.M. — ^Temperature  38.0.  Mucous  diarrhea. 

2:00        — Temperature  38.0.  Mucous  diarrhea  and  bile-stained  vom- 

itus. 

2:30        — ^Temjjerature  37.7.  Vomitus  and  diarrhea,  prostration. 

3:15         — ^Temperature  37.6.  Prostration.  Pulse  very  weak. 

3:50        — Temperature  36.8.  Condition  unchanged. 

4:50        — ^Temperature  36.4.  Profound  intoxication. 

5 :20  — Death  and  autopsy  immediately. 
Blood  obtained  in  oxalate  solution  showed  practically  no  plasma  on 
standing.  This  blood  concentration  is  very  common  in  severe  proteose 
intoxication.  Thorax,  heart,  and  lungs  normal.  Liver,  spleen,  pancreas, 
and  kidneys  are  swollen  and  engorged  with  blood.  Stomach  shows  a  pale 
pyloric  mucosa  and  pink  swollen  cardiac  mucosa.  Mucous  secretion  is 
very  abundant.  Duodenum,  jejunum,  and  ileum  present  a  deep  purple 
velvety  mucosa  coated  with  a  thick  layer  of  mucus.  Colon  shows  definite 
engorgement.  This  autopsy  is  in  every  way  typical  of  acute  intoxication 
resulting  from  a  lethal  dose  of  the  proteose  obtained  from  an  obstructed 
intestine. 

This  experiment  confirms  in  every  respect  the  preceding  observa- 
tion. There  seems  to  have  been  little  destruction  or  loss  of  the  toxic 
proteose  and  its  toxicological  reaction  is  identical  with  that  of  the 
original  material  before  passage  through  the  intestinal  tract.  Such 
resistance  toward  the  digestive  enzymes  is  remarkable. 

Proteose  Absent  from  Feces.  Control  Experiment.  Dog  18-55.  Spaniel, 
small  adult  female.  Weight  19.3  pounds. 

Oct.  22,  1 1  A.M.  Ether  anesthesia  and  intravenous  injection  of  proteose 
extract  obtained  Jrom  Dog  18-8.  Fecal  material  of  Oct.  8tb.  120  c.c.  total 
amount  obtained  as  described  above.  This  injection  caused  a  transient  fail 
in  blood  pressure,  but  no  change  in  the  temperature  curve.  There  were  no 
clinical  signs  of  intoxication  at  any  time. 

These  control  feces  contained  no  toxic  material  in  any  way  com- 
parable to  the  material  isolated  and  tested  in  the  two  preceding 
experiments.  These  feces  were  collected  from  the  same  dog,  18-8, 
with  the  exception  that  milk  was  given  by  stomach  tube  instead  of 
the  proteose  solution.  This  experiment  gives  the  necessary  control 


INTOXICATION  OF  INTESTINAL  OBSTRUCTION     1071 

to  the  two  preceding  observations  and  substantiates  other  observa- 
tions to  show  that  the  normal  intestinal  tract  contains  no  toxic 
proteose  material. 

Proteose  Isolated  Jrom  Colon  Loop  Material  Non-toxic.  Dog  19-19. 
Mongrel,  adult  male.  Weight  23.3  pounds. 

Aug.  13th,  12  M.  Ether  anesthesia  and  intravenous  injection  of 
proteose  extract  obtained  Jrom  the  colon  loop  material  of  Dog  18-8.  The 
entire  proteose  extract  made  as  described  above,  concentrated  to  100  c.c, 
given  slowly  intravenously.  This  injection  caused  only  a  slight  fall  in 
blood  pressure  with  considerable  flushing  of  the  skin.  It  caused  no  tem- 
perature reaction  of  any  appreciable  degree  and  not  the  slightest  evidence 
of  clinical  intoxication. 

Compare  with  the  several  experiments  given  just  below  to  show 
that  these  colon  loops  are  non-toxic  and  do  not  form  toxic  proteose- 
like  substances. 

Closed  Loop  oj  Colon.  Duration  Four  Months.  No  Intoxication.  Dog 
17-111.  Airedale,  young  adult  female.  Weight  22  pounds. 

Jan.  3d.  Dr.  Woolsey  isolated  a  closed  loop  of  the  colon  as  described 
above  and  established  the  intestinal  tract  by  anastomosis  between  the 
ileum  and  the  rectum. 

Jan.  5th  to  8th.  Normal  recovery.  Weight  19.3  pounds. 

Feb.  2d.  Dog  normal  and  regaining  lost  weight.  Weight  21.8  pounds. 

May  I  St.  Dog  has  been  uniformly  in  good  condition.  Weight  27.8 
pounds.  There  has  been  no  evidence  of  any  intoxication  at  any  time.  Dr. 
Woolsey  and  Dr.  Kerr  excised  the  loop  oJ  colon  with  no  operative  difficulty. 

Loop  of  Colon  includes  i  inch  of  ileum  which  is  empty.  The  cecum  is 
empty.  The  lower  end  of  the  colon  loop  contains  a  large  sausage-like  mass 
which  has  the  general  appearance  and  consistency  of  normal  feces.  It  is 
uniform  and  pasty  throughout  and  separates  cleanly  from  a  normal  pale 
mucous  membrane.  The  lower  end  of  the  colon  where  inverted  shows  one 
tiny  ulcer,  not  over  2  mm.  in  diameter.  Without  exception  the  mucosa 
elsewhere  is  pale,  normal,  and  intact.  The  microscope  shows  a  normal 
mucous  membrane  except  for  the  tiny  superficial  ulcer  described  above. 
Goblet  cells  and  mucus  are  conspicuous. 

Colon  Loop  Material  (about  150  grams  in  weight).  It  was  ground  with 
water  and  sand  to  a  thin  soupy  mixture,  the  final  volume  about  400  c.c 
This  was  not  centrifuged,  but  poured  direct  into  five  volumes  of  95  F>er 
cent  alcohol.  The  alcoholic  precipitate  dissolved  in  water  (about  1200  c.c.) 


1072    INTOXICATION  OF  INTESTINAL  OBSTRUCTION 

slightly  acidified  with  acetic  and  brought  to  a  boil.  The  precipitate  was 

removed  by  means  of  the  centrifuge,  giving  a  grayish  opalescent  fluid 

somewhat  like  clam  broth.  This  material  was  neutralized  and  tested  out 

upon  a  number  of  normal  puppies. 

Material  Jrom  Closed  Loop  oj  Colon.  Dog  17-1 1 1.  Tested  by  intravenous 

injection  upon  the  following  animals: 

Pup  17-207.  Weight  14  pounds.  2  c.c.  per  lb.  intravenously.  No  intoxica- 
tion. 

Pup  17-181.  Weight  14.3  pounds.  7  c.c.  per  lb.  intravenously.  No  intoxi- 
cation. 

Pup  17-217.  Weight  10.3  pounds.  8  c.c.  per  lb.  intravenously.  Slight  in- 
toxication. 

This  last  exj>eriment  (Pup  17-217)  showed  a  little  clinical  intox- 
ication and  slight  febrile  reaction.  The  amount  injected  was  very 
large  for  a  small  puppy,  but  it  may  indicate  a  trace  of  toxic  material 
in  this  closed  loop. 

Proteose  Absent  in  Feces  after  Colon  Extirpation.  Dog  18-42.  Fox- 
terrier,  adult  female.  Weight  12.8  pounds. 

Sept.  27th,  12:30  P.M.  Ether  anesthesia  and  intravenous  injection  of 
proteose  extract  obtained  Jrom  feces  of  Dog  17-111.  Thin  yellow  feces  (123 
grams  in  weight)  obtained  fresh  from  cage,  ground  up  and  extracted  with 
400  c.c.  distilled  water,  agitated  in  shaking-machine  for  five  hours  and 
separated  by  centrifuge.  The  opalescent  yellowish  broth-like  fluid  poured 
into  five  volumes  of  95  per  cent  alcohol.  After  two  days  the  alcoholic  pre- 
cipitate extracted  as  usual  with  water,  acidified,  brought  to  a  boil,  filtered, 
and  concentrated  over  the  water-bath  to  150  c.c.  The  final  solution  was 
almost  clear,  pale  amber  in  color.  Total  amount  of  this  extract  was  given 
intravenously  with  definite  but  moderate  depression  of  the  blood  pressure. 
There  was  a  slight  febrile  reaction,  but  no  definite  clinical  shock  and  no 
signs  of  the  usual  intoxication. 

This  experiment  gives  confirmatory  data  to  show  that  toxic 
proteoses  are  not  present  in  the  small  intestine  of  the  dog.  The  colon 
extirpation  makes  the  collection  of  soft  feces  very  easy  and  excludes 
the  possibility  of  any  neutralizing  action  taking  place  in  the  colon. 

Discussion.  The  experiments  outlined  above  are  capable  of  but 
a  single  interpretation.  It  is  quite  clear  from  these  experiments  and 
other  similar  observations  which  need  not  be  recorded  at  this  time, 
that  closed  colon  loops  are  never  associated  with  any  definite  clin- 


INTOXICATION  OF  INTESTINAL  OBSTRUCTION     1073 

fcal  intoxication  referable  to  the  closed  loop.  This  is  very  different 
from  closed  loops  of  the  small  intestine  which  invariably  are  asso- 
ciated with  distinct  evidences  of  intoxication.  Closed  loops  of  the 
colon  cause  no  disturbance  even  if  isolated  for  many  months  (four 
to  ten  or  longer).  Material  accumulates  slowly  in  these  loops,  and 
this  material  looks  remarkably  like  normal  fecal  material.  It  is  made 
up  mainly  of  cell  debris  and  masses  of  bacteria.  No  toxic  proteose 
material  can  be  isolated  from  this  colon  loop  material.  Again,  this 
differs  from  the  material  which  accumulates  in  a  closed  loop  of 
small  intestine  as  such  material  is  rich  in  toxic  proteose.  It  is  obvious, 
therefore,  that  the  colon  cannot  take  any  active  part  in  the  intoxica- 
tion of  intestinal  obstruction. 

The  proteose  material  isolated  from  an  obstructed  intestine  or 
closed  intestinal  loop  is  known  to  be  resistant  to  digestion  in  vitro 
(5).  These  experiments  show  conclusively  that  this  same  proteose 
material  can  resist  the  digestive  enzymes  of  the  intestinal  tract  of 
the  dog  for  forty-eight  hours  or  longer.  It  is  possible  to  recover  this 
proteose  from  the  feces  after  its  administration  by  stomach  tube. 

These  experiments  give  more  evidence  to  prove  that  these  toxic 
proteoses  are  not  present  in  the  small  intestine  of  the  normal  dog. 
A  study  of  the  fecal  material  obtained  from  dogs  whose  colons 
have  been  removed  shows  that  a  toxic  proteose  is  not  present  in  the 
small  intestine  and  excludes  any  neutralizing  action  on  the  part 
of  the  colon. 

BIBLIOGRAPHY 

1.  Whipple,  Stone,  and  Bernheim,  J.  Exper.  M.,  1914,  XIX,  166. 

2.  Davis,  D.  M.,  Johns  Hopkins  Hasp.  Bull.,  1914,  XXV,  33. 

3.  Whipple,  Rodenbaugh,  and  Kilgore,  J.  Exper.  M.,  19 16,  XXIII,  123. 

4.  Whipple  and  Van  Slyke,  J.  Exper.  M.,  1918,  XXVIII,  213. 

5.  Whipple,  Stone,  and  Bernheim,  J.  Exper.  M.,  19 13,  XVII,  307. 


SOME  EXPERIENCES  AND  OBSERVATIONS  IN  THE 
TREATMENT  OF  ARTERIOVENOUS  ANEURYSMS 

BY  THE  INTRASACCULAR  METHOD  OF  SUTURE  (eNDOANEURYS- 
MORAPHY),  with  special  REFERENCE  TO  THE  TRANS- 
VENOUS   ROUTE,    (a   summary) 

By  Rudolph  Matas,  M.D.,  Tulane  University,  New 
Orleans,  La. 

WITHOUT  attempting  a  general  discussion  on  the  treat- 
ment of  arteriovenous  aneurysms,  which  would  be  be- 
yond the  scope  of  this  contribution,  it  is  my  purf>ose  to 
give  a  brief  account  of  a  group  of  personal  experiences  which  illus- 
trate the  practical  application  of  the  intrasaccular  methods  of 
suture  which  I  have  so  long  advocated  for  the  cure  of  arterial  an- 
eurysms (endoaneurysmoraphy),  and  which  I  have  found  equally,  if 
not  more,  advantageous,  in  the  cure  of  arteriovenous  aneurysms. 
Of  course  there  is  no  single  method  or  technic  that  is  applicable 
to  all  varieties  of  arteriovenous  aneurysms  as  these  are  met  in 
practice.  There  are,  and  always  will  be,  cases  in  which  the  conserva- 
tive principle  of  the  suture,  which  aims  at  the  restoration  of  the 
functional  integrity  of  the  blood  vessels,  will  have  to  yield,  in  the 
presence  of  insurmountable  and  forbidding  anatomical  and  patho- 
logical conditions,  to  the  radical  methods  of  ligation  and  extirpation, 
which  are  also  to  be  regarded  as  conservative  whenever  they 
accomplish  their  purpose  (cure)  without  sacrifice  of  limb  or  life. 
But  the  experience  of  the  author  confirms  the  opinion  that  by  the 
adoption  of  new  technical  suggestions,  such  as  exhibited  in  this 
paper,  the  opportunities  for  the  application  of  a  conservative 
technic  can  be  much  enlarged,  thereby  reducing  very  considerably 
the  number  of  radical  ligations  and  extirpations  which  are  undoubt- 
edly performed  with  unnecessary  frequency  and  severity  in  the  cur- 
rent practice  of  the  day. 

It  would  be  well  to  premise  a  further  consideration  of  this 

1074 


TREATMENT   OF  ARTERIOVENOUS  ANEURYSMS      1075 

subject  by  stating  that  in  dealing  with  the  latest  suggestions  pre- 
sented in  these  personal  experiences,  we  have  in  mind  the  treatment 
of  the  fully  formed  or  established  types  of  the  mature  arteriovenous 
lesions  as  distinguished  from  the  primary  or  recent  wounds  of  these 
vessels,  when  the  question  of  primary  hemostasis  for  hemorrhage  or 
the  relief  of  rapidly  spreading  hematomas  are  the  first  consideration. 
Even  in  these,  the  principle  of  conserving  the  functional  integrity 
of  the  injured  vessels  is  seriously  to  be  considered,  and  can  be 
successfully  met,  in  many  instances,  by  the  devices  of  conservative 
practice — such  as  end-to-end  suture  of  the  vessels,  vascular  grafts, 
and  intubation  with  paraffined  glass  or  metallic  tubes  (Brewer's, 
Tuffier's,  Lespinasse's,  et  als.).  But  the  technical  problems  are  very 
diflferent  from  those  offered  by  the  mature  or  established  arterio- 
venous aneurysms. 

If  we  were  to  study  clearly  the  morphology  and  pathological 
anatomy  of  the  more  mature  and  fully  established  arteriovenous 
aneurysms,  we  would  probably  be  able  to  differentiate  more  than 
twenty  varieties.  These,  however,  can  be  grouped  about  the  two 
fundamental  types,  which  have  been  classical  since  the  days  of 
Wm.  Hunter  and  Scarpa.  These  are  the  aneurysmal  varix  (Varix  aneu- 
rysmaticus)  and  the  varicose  aneurysm  (aneurysma  varicosum).  The 
aneurysmal  varix,  with  its  sub  varieties,  typifies  the  direct  mode  of 
arteriovenous  anastomosis;  the  varicose  aneurysm,  the  indirect 
communication  between  the  two  vessels,  through  a  common  or 
intermediary  sac.  In  the  aneurysmal  varix  the  arterial  and  venous 
wounds  become  agglutinated  and  adherent  as  a  direct  inosculation, 
following  as  an  immediate  or  early  sequel  of  the  injury,  and  an 
arteriovenous  fistula  is  established  after  the  small  perivascular  ex- 
travasation has  been  absorbed.  Two  important  sub  varieties  of  this 
type  must  be  distinguished:  (i)  The  true  aneurysmal  varix  which 
presupposes  a  varicose  dilatation  of  the  vein,  constituting  the  sac 
of  the  aneurysm,  and  which,  owing  to  the  progressive  dilatation 
of  the  vein,  may  attain  enormous  proportions,  not  only  at  the  seat 
of  the  anastomosis,  but  far  beyond  the  proximal  and  distal  sides  of 
the  abnormal  communication;  and  (2)  the  simple  arteriovenous 
fistula  {pblebartery  of  Broca),  in  which  there  is  no  varicose  dilatation 
except  a  general  symmetrical  enlargement  or  ampullar  formation  of 
the  vein  at  the  site  of  the  fistula. 


1076      TREATMENT  OF  ARTERIOVENOUS  ANEURYSMS 

In  the  varicose  aneurysm,  as  classically  described,  the  normal 
anatomical  position  of  the  vessels  is  disturbed;  they  do  not  lie  side 
by  side  as  in  the  aneurysmal  varices.  The  injury  is  followed  by  more 
or  less  extensive  hemorrhage  which,  being  circumscribed  by  the 
resistance  of  the  perivascular  tissues,  forms  a  well-defined  pulsating 
hematoma  and  finally  an  encysted  and  clearly  differentiated  and 
well-walled  sac,  which  is  lined  with  endothelium  continuous  with  that 
of  the  open  mouths  of  the  blood  vessels. 

As  above  stated,  it  is  customary  to  describe  a  varicose  aneurysm 
as  an  intermediary  sac  formed  and  interposed  between  the  injured 
vessels,  through  which  an  indirect  communication  is  established 
between  the  artery  and  vein.  But  contrary  to  this  teaching,  all 
surgeons  of  experience  will  agree  that  the  formation  of  this  inter- 
mediary sac  is  an  exceptional  occurrence,  whereas  the  presence  of  a 
well-defined  sac  into  which  the  injured  vessels  open  separately  with- 
out any  disturbance  in  their  anatomical  relations — the  two  vessels 
lying  side  by  side — is  a  common  occurrence.  On  opening  such  a  sac 
and  evacuating  the  clot,  the  two  vessels  will  be  seen  at  the  bottom 
or  at  some  part  of  the  periphery  of  the  cavity,  plainly  in  relief,  or 
faintly  outlined  under  the  fibro-endothelial  capsule,  which,  in  old 
aneurysms,  covers  them  like  a  veil.  The  orifices  indicating  the 
original  seat  of  injury  will  show  themselves  in  various  ways — either 
as  elliptical  or  slit-like  openings  lying  parallel  to  each  other,  or  as 
quadruple  groups,  two  proximal  and  two  distal,  separated  by  an 
interval  of  variable  length.  The  proximal  orifices  represent  the 
cardiac,  and  the  distal,  the  peripheral  ends  of  the  divided  vessels. 
These  different  appearances  depend  upon  the  extent  of  the  primary 
injury — whether  a  partial  or  a  total  division  of  the  vessels  is  in- 
volved in  the  trauma.  In  some  rare  cases,  in  which  the  vessels  have 
been  completely  divided,  there  are,  as  Amussat  first  observed,  only 
two  recognizable  openings  leading  into  the  sac,  one  for  the  artery 
and  one  for  the  vein,  which  indicate  the  cardiac  or  central  ends  of 
the  divided  blood  vessels,  the  peripheral  ends  having  been  occluded 
by  thrombi  and  finally  lost  in  the  wall  of  the  sac.  It  is  more  frequent, 
in  our  experience,  to  see  a  type  of  varicose  aneurysm,  following 
partial  division  of  the  vessels,  in  which  there  is  a  common,  fairly 
large  sac,  which,  when  opened,  exhibits  a  smaller  pocket  formed  by 
the  sheath  of  the  vessels.  In  the  center  of  this  smaller  cavity  four 


TREATMENT  OF  ARTERIOVENOUS  ANEURYSMS      1077 

orifices  appear  in  close  proximity,  showing  that  the  vessels  have  been 
injured  tangentially  and  simultaneously,  either  by  stab  or  shot — 
causing  no  disturbance  in  their  relations,  as  they  lie  side  by  side  in 
perfect  apposition.  The  four  orifices  fie  parallel  to  each  other,  two 
above  and  two  below,  and  open  directly  into  the  smaller  sac  formed 
by  the  sheath  which  has  been  torn  open,  leaving  a  circular  or 
elfiptical  opening  which  merges  in  its  contour  with  the  larger  pseudc 
sac  formed  by  the  primary  hematoma. 

The  margins  or  orifices  in  all  types  of  arteriovenous  aneurysms 
of  mature  formation  (six  or  eight  weeks,  and  over)  are  usually  thick 
and  smooth,  and  are  covered  by  a  gfistening  endothefium  which 
merges  and  is  continuous  with  the  endothefial  fining  of  the  cyst-fike 
cavity  of  the  sac.  The  same  blending  or  merging  with  the  endothefial 
fining  is  observed  in  the  fistulous  communications  existing  in  the 
direct  arteriovenous  lesions,  a  matter  of  importance,  as  this  thick- 
ened and  firm  fining  offers  an  excefient  grip  for  the  sutures  which 
obfiterate  the  anastomotic  communications. 

Another  and  most  troublesome,  but  rarer,  type  is  the  arterio- 
venous aneurysm  in  which  the  artery  has  been  injured  simultane- 
ously with  its  two  sateHite  veins.  In  these  cases  a  venous  sac  or 
ampulla  is  formed  on  each  side  of  the  artery.  The  two  venous 
sacs  are  usuaHy  asymmetrical,  according  to  the  different  planes 
of  resistance  encountered  in  their  development,  one  of  these  attain- 
ing large  proportions,  and  the  dimensions  of  the  other  being  only 
moderate. 

In  other,  still  rarer,  cases,  more  often  met  in  civil  practice 
(hunting  accidents),  and  fortunately  fimited,  usuaUy,  to  the  periph- 
eral vessels  of  a  secondary  order  (upper  extremity),  are  those  in 
which  an  artery  is  injured  simultaneously  and  at  many  places  by 
fine  shot.  In  these  cases  the  condition  imitates  cirsoid  aneurysm, 
and  the  arteries  and  veins  are  mixed  up  in  such  inextricable  confu- 
sion that  extirpation  is  the  only  remedy;  fortunately  they  seldom 
attain  dangerous  proportions  or  cause  serious  disabifities,  and  can 
be  safely  allowed  to  remain  undisturbed. 

Arteriovenous  aneurysm  with  an  arterial  sac,  in  which  the  aneu- 
rysm ruptures  into  a  vein,  is  so  great  a  rarity  in  surgical  practice 
that  it  can  well  be  relegated  to  the  domain  of  pure  pathology.  It 
is  practicaHy  observed  only  in  the  thorax  as  a  result  of  pathological 


loyS     TREATMENT  OF  ARTERIOVENOUS   ANEURYSMS 

conditions  beginning  on  the  arterial  side  (aortic  aneurysm  opening 
into  the  vena  cava,  etc.). 

Personal  Experience  with  the  Suture  in  Arteriovenous  Aneurysms.  In 
a  personal  experience  of  over  204  surgical  interventions  upon  the  large 
blood  vessels,  I  find  the  record  of  24  cases  of  arteriovenous  injuries  of 
various  types.  In  this  group  I  have  utihzed  the  principle  of  endoaneurys- 
moraphy  in  12;  viz.,  common  carotid  (i);  external  iliac  (i);  the  common 
and  superficial  femoral  (8);  the  peroneal  vessels  (i);  the  subclavian  (i). 
All  of  these  have  made  good  recoveries,  except  the  carotid  aneurysm,  in 
which  death  occurred  on  the  eighth  day  after  the  operation,  from  coronary 
disease  and  pulmonary  clot;  and  in  the  iliac  aneurysm,  in  which  death 
occurred  from  mesenteric  thrombosis  and  gangrene  of  the  bowel  caused 
by  prolonged  compression  of  a  loop  of  bowel  by  a  powerful  Doyen  retractor, 
which  had  been  used  in  an  extensive  subperitoneal  dissection  to  expose  the 
iliac  vessels.  In  neither  case,  as  shown  by  autopsy,  was  the  technic  of  the 
operation,  as  far  as  the  vessels  were  concerned,  responsible  for  the  fatal 
termination,  as  the  condition  of  the  wound  was  found  to  be  faultless.  In 
the  subclavian  case,  which  was  performed  September  3,  1900,  on  a  young 
white  farmer,  age  twenty-four  years,  the  artery,  which  had  been  perforated 
with  a  bullet  in  the  second  division,  immediately  behind  the  anterior  sca- 
lene, had  to  be  ligated  on  each  side  of  the  muscle;  but  the  vein,  which  was 
surprisingly  small,  was  sutured.  The  patient  recovered,  but  lost  part  of 
his  hand  from  arterial  ischemia  and  necrosis. 

Lateral  Angiorapby  in  Arteriovenous  Hematoma.  In  another  case,  a  white 
man,  age  twenty-six  years,  operated  at  the  Touro  Infirmary  on  May  3,  1907, 
suffered  a  gunshot  wound  involving  the  femoral  vessels  in  Hunter's  canal, 
and  was  operated  upon  about  six  weeks  after  the  injury,  by  separate  lateral 
suture  of  each  one  of  the  orifices,  leaving  the  lumen  of  each  vessel  pervious. 
The  patient  made  an  excellent  recovery,  with  perfect  functional  result  to 
the  limb,  notwithstanding  his  deplorable  condition  from  many  wounds, 
including  multiple  fractures  of  the  lower  jaw,  which  he  had  received  in 
quelling  a  negro  riot  at  Liberty,  Miss.  This  procedure  represents  probably 
the  oldest  and,  undoubtedly,  the  best-known  of  the  conservative  operations 
that  have  been  applied  for  the  cure  of  arteriovenous  aneurysms,  and  is  an 
ideal  method  when  it  can  be  carried  out.  The  experience  of  the  recent  war 
will,  no  doubt,  add  quite  a  large  number  of  such  cases  to  the  early  list 
of  the  pioneers  (Z.  von  Manteuffel  (1895),  femoral  vessels;  Cammagio 
(1898),  femoral  vessels;  Gerard  Marchant  (1898),  brachial  suture;  Peugniez 
(1900),  Matas  (1900),  subclavian  suture),  and  other  civilian  and  military 
surgeons  who  have  availed  themselves  of  the  progress  in  vascular  surgery 
at  the  present  day. 


TREATMENT   OF  ARTERIOVENOUS  ANEURYSMS     1079 

TbeObliterative  Suture  in  Arteriovenous  Aneurysm.  Another  case,  operated 
on  March  8, 1912,  was  that  of  a  youth  of  eighteen  years  from  Wesson,  Miss., 
who  had  been  accidentally  stabbed,  when  twelve  years  old,  with  a  long 
pocket  knife,  in  the  upper  femoral  region.  He  had  developed  an  arterio- 
venous aneurysm  which  involved  the  common  femoral  vessels  at  the  apex 
of  Scarpa's  triangle,  close  to  the  origin  of  the  profunda.  In  view  of  the  long 
duration  and  possible  necessity  of  doing  an  obliterative  oF>eration,  the  boy 
was  kept  under  careful  observation  for  two  weeks  before  the  op>eration. 
During  this  time  he  was  well  nourished  and  given  digitalis  systematically, 
in  the  hope  of  increasing  his  blood  pressure,  which  was  scarcely  ever  over 
no  S.  Frequent  tests  were  made  of  his  collateral  circulation,  which 
showed  that  the  living  color  returned  to  the  limb  after  Esmarch  is- 
chemia, while  the  common  femoral  was  compressed.  The  living  color  re- 
turned in  about  five  minutes,  but  just  before  the  op)eration  the  time  had 
shortened  to  three  minutes.  Feeling  that  a  good  collateral  circulation  had 
been  established,  I  undertook  the  operation,  believing  that,  if  it  became 
necessary,  an  obliteration  could  be  performed  without  risk  to  the  limb.  The 
operation  was  performed  under  ether  at  the  Touro  Infirmary  on  March  8, 
1912.  The  incision,  directly  into  the  sac,  revealed  a  large,  well-Iined  cavity 
which  was  at  first  taken  to  be  the  dilated  femoral  vein,  but  which  was  subse- 
quently interpreted  as  a  pseudo  sac  well  lined  with  endothelium,  which 
opened  directly  into  a  lesser  pocket  of  oval  shape,  measuring  about  2  inches 
in  diameter.  At  the  bottom  of  this  could  be  seen  four  separate  orifices,  each 
large  enough  to  admit  the  tip  of  the  little  finger  and  grouped  into  a  quadri- 
lateral, the  two  openings  on  the  inner  side  corresponding  to  the  distal  and 
proximal  orifices  of  the  femoral  vein  and  the  two  outer  to  those  of  the  artery. 
A  ridge  or  linear  induration  indicated  the  original  septum  of  the  sheath 
which  separated  the  arterial  from  the  venous  compartment,  but  the  edges 
of  the  orifices  were  continuous  and  blended  with  the  septum  and  with  the 
smooth,  glistening  endothelial  surface  that  lined  the  interior  of  the  sac. 
Each  one  of  these  orifices  was  now  sutured  separately  with  fine  paraffined 
linen,  leaving  it  completely  sealed  and  obliterated.  Then  all  communi- 
cations leading  from  the  large  vessels  to  the  sac  were  closed.  The  sac,  which 
was  very  densely  incrusted  all  over  its  walls  with  calcareous  deposits  in 
plaques,  was  cleared  of  these  incrustations  only  by  prolonged  scrubbing 
with  saline  solution  and  gauze  sponges.  In  the  main  cavity,  which  formed 
the  bulk  of  the  aneurysm  (size  of  a  small  apple),  a  mass  of  phleboliths  was 
found  in  the  midst  of  the  red  clot.  After  the  toilet  of  the  sac  had  been  com- 
pleted, this  was  obliterated  partially  by  plication  and  by  infolding  of  the 
sac  walls  with  continued  rows  of  fine  chromic  gut  sutures.  The  blood  pres- 
sure before  the  operation  (9.40  a.m.)  was  no  S.;  during  the  op>eration  it 


io8o     TREATMENT  OF  ARTERIOVENOUS   ANEURYSMS 

rose  to  120  S  and  at  the  close  of  the  operation  (10.25  a.m.)  it  fell  again  to 
no  S.  At  the  close  of  the  operation  the  Esmarch  constrictor,  which  had 
been  applied  high  up  in  the  groin,  was  removed  and  was  followed,  in  less 
than  one  minute,  by  a  return  of  a  good  living  color  throughout  the  ex- 
tremity to  the  tip  of  the  toes.  At  10.35  a.m.  the  dorsalis  pedis  and  posterior 
tibial  could  be  felt  beating  distinctly  in  the  foot.  Evidently,  the  preliminary 
tests  of  the  collateral  circulation  had  told  the  truth,  and  the  results  con- 
firmed our  confidence  in  their  value,  and  justified  the  obliterative  operation 
which  we  had  adopted. 

The  records  show  that  the  wound  healed  per  primam.  It  was  inspected 
on  the  fourth  day.  An  ulcer  which  had  existed  in  the  leg  as  a  consequence 
of  the  varicosities  healed  rapidly,  and  the  boy  was  discharged  and  returned 
to  his  home  on  March  29th,  nineteen  days  after  the  operation,  with  his  ulcer 
healed,  a  notable  reduction  in  the  varicosities,  and  perfect  functional  use 
of  the  limb. 

Since  the  day  of  his  discharge  I  have  seen  the  boy  repeatedly,  and  in 
my  last  examination,  one  year  ago,  there  was  no  trace  of  the  aneurysm, 
and  only  a  linear  scar  indicated  the  site  of  the  operation.  The  varicosities 
along  the  saphenous  tract  had  subsided,  the  ulcer  had  remained  healed, 
and  even  the  pigmentation  which  had  darkened  his  leg  had  paled.  He  was 
working  on  a  farm  and  doing  hard  labor  as  a  field  hand. 

This  case  illustrates  not  only  the  simplicity  and  safety  of  the 
technic  of  the  intrasaccular  suture  in  its  obliterative  phases,  but  its 
successful  application  to  a  type  of  varicose  aneurysms,  which  is  not 
infrequent  and  could  be  made  quite  formidable  if  attacked  by 
followers  of  the  methods  of  either  one  of  the  extreme  and  divergent 
schools  of  vascular  surgery, — the  ultra  conservatives,  represented, 
on  the  one  hand,  by  the  German  followers  of  Lexer  (the  large 
majority  of  the  German  military  operators  in  the  late  war),  who 
believe  it  is  their  duty  to  do  the  so-called  "ideale"  operation  in 
every  case  in  which  it  is  feasible,  and  who,  taking  this  case  as  an 
example,  would  have  systematically  extirpated  the  sac,  dissected 
out  the  vessels  from  their  bed  and  attempted  to  do  an  end-to-end 
suture  of  both  vessels;  and,  on  the  other  hand,  the  ultra  radicals, 
represented  by  the  French  school  of  surgeons  who,  following  the 
lead  of  Delbet,  extirpate  the  sac,  together  with  its  vascular  contents, 
and  then  ligate  the  four  stumps  by  the  quadruple  ligature. 

Between  these  stand  the  intrasaccular  ligaturists  of  the  British 
and  Japanese  schools,  who  do  far  less  damage  to  the  perivascular 


TREATMENT   OF  ARTERIOVENOUS  ANEURYSMS     1081 

tissues,  but  who,  none  the  less,  give  themselves  unnecessary  worry 
and  complicate  their  technic  by  dissecting  out  the  vessels  in  order 
to  close  them  by  the  quadruple  ligature. 

It  is  possible  that  by  any  one  of  these  methods  this  aneurysm 
would  have  been  cured  and  the  limb  saved,  because,  in  this  case, 
it  had  been  clearly  demonstrated  that  the  collateral  circulation  had 
been  established  and  that  restorative  procedures  were  unnecessary. 
But  why  undertake  the  laborious  and,  at  best,  uncertain  procedure 
of  a  vascular  angioraphy,  as  in  the  so-called  "ideale"  operation, 
or  subject  the  patient  to  the  unnecessary  trauma  of  an  extirpation 
with  its  waste  of  good  vascular  material;  or,  again,  the  extrasac- 
cular  dissection  required  by  quadruple  ligature — when  the  simple 
obHteration  of  the  orifices  can  be  so  easily  accomplished,  with  so 
much  economy  to  the  blood  vessels  (including  the  collaterals) — and 
the  objective  attained  so  easily  and  safely,  by  the  elementary  technic 
of  the  suture?  j.   fit 

I  could  easily  add  to  the  testimony  of  the  preceding  case  by  a  ^^^^ 
number  of  clinical  experiences  which  prove  the  simplicity  and  re- 
liability of  the  endoaneurysmal  suture  in  the  many  phases  of  vari- 
cose aneurysm  in  which  the  obliterative  principle  is  indicated.  Apart 
from  my  own  experiences,  I  could  quote  a  number  of  confirmatory 
published  reports  from  the  practice  of  my  associates  and  other  local 
surgeons  (Drs.  Gessner,  Parham,  Maes,  Danna,  Lafferty,  and  others) 
who  have  adopted  the  endoaneurysmal  suture  and  successfully 
applied  it  in  the  treatment  of  arteriovenous  lesions. 

But  I  must  proceed  with  the  treatment  of  that  most  familiar 
type  of  arteriovenous  injury,  the  aneurysmal  varix  or  fistula,  which 
has  furnished  me  with  the  largest  and  most  varied  experience  in  nine 
cases,  in  all  of  which  I  have  applied  the  principle  of  the  endoaneurys- 
mal suture  in  its  restorative  phases,  with  a  success  that  could  scarcely 
have  been  obtained  by  any  one  of  the  conservative  or  radical  pro- 
cedures in  vogue. 

In  order  to  approach  this  subject  more  intelligently,  a  brief 
reference  to  the  historical  evolution  of  the  special  modification  of 
the  endoaneurysmal  method,  as  adapted  to  the  peculiarities  of 
aneurysmal  varices,  is  necessary. 

Endoaneurysmal  Suture  by  the  Transvenous  Route.  In  the  Annals 
of  Surgery  for  February,  1903,  I  published  my  first  systematic  ac- 


io82     TREATMENT   OF  ARTERIOVENOUS  ANEURYSMS 

count  of  the  endoaneurysmal  method  of  suture  which  I  had  first 
applied  to  a  brachial  aneurysm  on  March  30,  1888.^ 

My  paper  dealt  with  arterial  aneurysms  and  not  with  arterio- 
venous lesions,  though  the  indications  for  the  suture  in  these  cases 
were  obvious.  This  gap  in  the  technic,  however,  was  quickly  filled 
by  my  friend  and  former  associate.  Dr.  W.  S.  Bickham  of  New 
York,  who  in  an  excellent  paper  published  in  the  Annals  of  Surgery 
for  May,  1904,  suggested  and  elaborated  a  most  ingenious  technic 
for  the  application  of  the  intrasaccular  suture  to  the  various  lesions 
grouped  together  under  the  name  of  arteriovenous  aneurysms. 

The  methods  suggested  and  so  clearly  illustrated  by  Dr.  Bickham 
in  1904  will  be  found  more  systematically  described  in  his  excellent 
"Text  Book  of  Operative  Surgery"  (Third  Edit.,  Saunders,  1908), 
under  the  heading  of  "Operations  for  the  Radical  Cure  of  Arterio- 
venous Aneurysms  with  Preservation  of  the  Circulation  in  the 
Artery  and  Vein:  (The  Matas-Bickham  Operation)." 

Bickham's  foresight  and  planning  of  this  technic  based  upon  the 
theoretical  possibilities  offered  by  the  most  familiar  types  of  arterio- 
venous aneurysms  is,  indeed,  most  remarkable  and  praiseworthy. 

The  first  clinical  application  of  one  of  Bickham's  suggestions, 
viz.,  to  attack  the  problem  of  closing  the  fistula  in  aneurysmal 
varix  by  the  transvenous  route,  was  first  demonstrated  clinically 
by  my  friend  and  associate,  Dr.  H.  B.  Gessner,  in  the  case  of  a 
colored  laborer,  age  twenty-two  years,  who  had  sustained  a  gunshot 
injury  (multiple  small  shot)  in  the  abdomen  and  right  thigh.  The 
injury  had  been  inflicted  eleven  years  previously  and  involved  the 
femoral  vessels  in  Hunter's  canal.  The  injury  had  caused  com- 
paratively little  disturbance.  The  operation  was  performed  on  May 
30,  1908.  The  sac  itself  was  small,  and  notwithstanding  the  long 
duration  of  the  injury,  there  were  none  of  the  varicosities  or  trophic 
changes  in  the  skin  of  the  lower  extremity  which  characterize  the 
progressive  types  of  varix  aneurysmaticus.  The  thrill  and  murmur 
caused  the  patient  anxiety,  and  this  was  the  chief  reason  for  the 
intervention.  In  this  case  the  sac  was  formed  by  ampullar  dilatation 
of  one  of  the  venae  comites,  the  other  being  intact.  Three  arterio- 
venous fistulae  caused  by  small  shot  were  discovered  in  the  interior 
of  the  venous  sac  when  this  was  opened.  They  were  all  closed  by 

» Med.  News,  Phila.,  October  27,  1888. 


Fig.  I.  Case  of  John  G.  (Jugulo- 
carotid  Aneurysm),  of  Fifteen  Years' 
Standing. 

Showing  great  plexus  of  tortuous, 
pulsating  superficial  veins  in  neck. 
Also  puftiness  of  left  face  and  corre- 
sponding exophthalmos. 


Fig.  2  (diagrammatic).  Showing  enormous 
dilatation  and  varicosities  of  superficial  ven- 
ous plexus  after  dissection.  (Case  of  John  G., 
Jugulo-carotid  Aneurysm.) 


Fig.   3.     Case  of  John  G.    (Jugulo-carotid  Aneurysm). 

Showing  the  relations  of  the  carotid  and  jugular.  The 
septum  separating  the  two  vessels;  the  anastomotic  com- 
munication. The  aluminum  bands  applied  to  the  artery 
and  vein  and  the  two  additional  ligatures  on  the  vein  above 
and  below  the  arteriovenous  fistula. 


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Fig.  1 8.  Shows  Interior  of  Large  Space  Occupied  by  Hematoma, 
Covered  Over  with  a  Veil  of  Semitranslucent  Exudate  in  Process  of 
Organization.   (J.  B.  Arteriovenous  Hematoma  of  Femoral  Vessels.) 

First  Stage  of  the  Suture.  The  Needle  is  shown  Penetrating  through  Both  Walls 
of  the  Artery  and  through  the  Arteriovenous  Septum,  so  as  to  Close  the  Narrow 
Fistula  which  Connected  Both  Vessels.  By  Lifting  the  Walls  of  the  Collapsed  and 
Thin  Vessels  with  Two  Traction  Sutures,  one  at  each  End,  the  Curved  Needle  was 
able  to  Penetrate  the  Septum  and  Obliterate  the  Orifice  in  the  Vein,  and  in  the 
Artery,  without  Obliteratmg  the  Lumen  of  the  Vein  and  only  Partially  that  of  the 
Artery.  The  Method  of  Closure  by  Suture  is  Shown  in  the  Insert  A  and  B. 


Fig.  19.  Shows  the  Result  of  the  Suture  (Paraffined  Silk). 

(J.  B.  Arteriovenous  Hematoma  of  Femoral  Vessels.) 

The  Suture  Closed  the  Fistula  and  Allowed  Blood  to  Circulate 
through  two  Narrow  Channels,  on  Each  Side  of  the  Line  of  Suture.  The 
Artery  Pulsated  very  Distinctly  after  Total  Suppression  of  the  Thrill 
and  Other  Signs  of  Arteriovenous  Fistula  had  been  Obtained.  The  Sac 
of  the  Hematoma  was  Obliterated  by  Allowing  theSartorius  to  Fill  the 
Space  after  Clearing  out  the  Clot.  Healing  per  Primam  and  Perfect 
Recovery. 


TREATMENT  OF  ARTERIOVENOUS  ANEURYSMS     1083 

separate   intrasaccular  sutures  and  the  artery   left    undisturbed. 
The  sac  itself  was  infolded  and  obliterated  by  suture. 

The  next  case  came  under  my  observation  in  19 12  and  gave  me 
the  opportunity  to  apply,  for  the  first  time,  Bickham's  suggestion 
of  the  transvenous  route  as  a  means  of  approach  to  an  arteriovenous 
fistula  in  a  typical  aneurysmal  varix  of  the  jugulo-carotid  tracts  of 
long  standing.  It  was  a  most  difficult  and  forbidding  case,  and  I 
do  not  see  how  I  could  have  accomplished  what  I  did  by  any  other 
method. 

Arteriovenous  Fistula  (Gunshot  of  Fifteen  Years'  Standing)  oj  the  Jugulo- 
carotid  Tracts,  at  the  Bifurcation.  Obliteration  of  the  Orifice  of  Communi- 
cation by  Direct  Suture  Applied  by  the  Transvenous  (Transjugular)  Route, 
Leaving  an  Open  Collateral  Channel  to  the  Brain  via  the  External  and 
Internal  Caroticb  and  the  Bifurcation.  (See  Fig.  i.)  The  patient,  John 
G.,  an  intelligent  negro  barber,  age  forty  years,  consulted  me  first  on 
April  12,  191 2.  He  had  been  shot  in  the  neck  fifteen  years  before  he  applied 
to  me  for  relief  of  symptoms  caused  by  an  aneurysmal  varix  which,  in  the 
course  of  these  years,  had  led  to  an  enormous  dilatation  of  the  jugular 
and  all  the  tributary  veins.  The  man  had  been  shot  in  an  altercation,  with 
a  revolver,  at  close  range,  and  the  bullet  (.38  caliber)  had  perforated  the 
internal  jugular  and  the  common  carotid  on  a  level  with  the  bifurcation. 
The  bullet,  as  was  discovered  fifteen  years  after,  had  lodged  in  the  back  of 
the  neck  and  could  be  seen,  in  the  radiograph,  behind  the  articular  process 
of  the  third  cervical  vertebra.  The  hospital  record  shows  that  one  hour 
after  the  injury  he  developed  unmistakable  signs  of  an  arteriovenous 
communication,  which  persisted  and  gradually  grew  worse  as  time  went  on. 
Simultaneously  with  the  bivascular  injury,  the  spinal  cord  had  been 
wounded.  From  this  injury  he  gradually  recovered  in  the  course  of  five 
years.  Also,  as  an  immediate  sequel  of  this  injury,  he  developed  a  traumatic 
meningitis,  with  hyperpyrexia  (107.6°)  which  kept  him  in  a  state  of  un- 
consciousness and  delirium  for  fifteen  days.  He  recovered  slowly,  but  was 
finally  discharged  from  the  hospital,  hemiplegic,  with  the  aneurysmal  varix 
in  full  activity.  Apart  from  the  annoying  thrill  and  great  noises  which  he 
heard  roaring  in  his  head,  he  was  fairly  comfortable  and  was  able,  at  the  end 
of  five  years,  to  return  to  his  trade  as  barber.  It  was  not  until  about  one 
year  before  his  consultation  with  me  that  the  aneurysm,  or,  at  least,  the 
swelling  in  his  neck,  grew  rapidly,  aud  he  began  to  suffer  with  dyspnea  and 
with  "choking  spells"  whenever  he  made  unusual  muscular  efforts.  He 
then  had  to  give  up  his  work  and  go  to  bed.  His  history  also  showed  that 
he  had  been  a  steady  drinker  and  a  syphilitic.  He  had  a  large  dilated  heart 


io84     TREATMENT  OF  ARTERIOVENOUS  ANEURYSMS 

and  aorta  with  an  aortic  obstructive  murmur,  an  irregular  pulse,  and  rela- 
tively low  blood  pressure.  He  was  a  stout  man,  weighing  over  212  pounds, 
and  his  neck  was  disproportionately  large  from  the  great  turgescence  and 
enormous  dilatation  and  tortuosity  of  the  superficial  veins,  which  pulsated, 
purred,  and  thrilled  like  living  things.  He  had  also  developed  a  left-sided 
exophthalmos  caused  by  the  dilatation  of  the  retrobulbar  veins,  which 
gave  him  a  very  striking  appearance. 

Whenever  he  exerted  himself  he  was  seized  with  dyspnea  and  a  great 
anxiety,  which  he  attributed  to  the  aneurysm,  as  the  veins  swelled  and 
formed  a  collar  which,  he  said,  "strangled  him." 

At  first,  I  would  not  consider  an  operation,  because  I  believed  the  car- 
diovascular lesions  were  so  advanced  that  they  would  soon  prove  fatal. 
However,  after  observing  him  for  one  month,  it  occurred  to  me  that  the 
dyspneic  spells  were,  in  part,  due  to  the  great  strain  imposed  upon  the 
right  heart  by  the  constant  inflow  of  the  enormous  stream  of  arterial  blood 
which  was  being  short-circuited  from  the  arterial  into  the  venous  system^ 
through  the  fistula,  at  the  abnormal  jugulo-carotid  junction.  For  nearly 
fifteen  years  his  heart  had  been  able  to  stand  the  strain  by  compensatory 
hypertrophy;  but  now,  in  consequence  of  myocardial  degenerative  changes, 
it  yielded  to  the  strain  at  the  slightest  provocation,  and  he  was  in  constant 
danger  of  an  acute  dilatation.  It  seemed  to  me  that  if  the  fistula  could 
be  closed,  the  great  strain  on  the  heart  would  be  relieved  and  his  gen- 
eral.  condition  improved.  Chiefly  for  this  reason  I  yielded  to  his  urgent 
solicitation,  but  with  grave  misgivings  as  to  the  outcome,  which  he  fully 
realized. 

The  Operation.  I  decided  that  I  would  operate  in  two  stages.  The  first 
was  to  be  limited  to  the  clearing  out  of  the  great  mass  of  superficial  veins 
which  were  in  the  way  and  prevented  a  free  access  to  the  common  carotid; 
then,  a  removable  aluminum  band,  of  the  type  that  we  had  been  using  for 
years  for  this  purpose  (Matas- Allen  band),  was  to  be  placed  on  the  artery 
with  a  view  of  testing  the  efficiency  of  the  collateral  circulation  in  the  brain, 
through  the  circle  of  Willis.  The  first  stage  was  to  end  with  this  step,  the 
wound  was  to  be  closed,  and  the  eff'ect  of  the  carotid  occlusion  on  the  brain 
was  to  be  observed  for  several  days.  If  no  complications  followed,  the  second 
stage  was  to  be  undertaken  in  a  few  days  with  a  view  of  closing  the  arterio- 
venous fistula  and  curing  the  aneurysm.  This  program  was  carried  out  to 
the  letter,  with  some  additions,  on  May  4,  19 12.  In  view  of  the  great  dangers 
of  general  anesthesia,  the  operation,  in  two  stages,  was  performed  under 
local  and  regional  anesthesia  with  novocain-adrenalin  solution,  preceded 
by  a  hypodermic  of  morphia  gr.  1/4  and  scopolamin  gr.  1/150. 

The  difficulties  of  the  operation  were  just  as  great  as  we  had  antici- 


TREATMENT  OF  ARTERIOVENOUS  ANEURYSMS      1085 

pated  and,  in  completing  its  first  stage,  two  hours  and  a  half  were  consumed 
in  one  of  the  most  difficult,  tedious,  and  trying  dissections  that  I  can  re- 
member in  all  my  surgical  experience.  We  were  greatly  assisted,  however, 
by  the  patient's  stoic  and  even  cheerful  attitude.  He  nerver  complained  and 
helped  us  at  all  times  by  placing  his  head  and  neck  in  the  most  favorable 
position  for  our  work.  In  this  way  we  were  able  to  clear  the  field  of  the 
immense  pulsating  and  squirming  plexus  of  the  veins  which  covered  the 
entire  field  from  the  submaxillary  region  to  the  sternum  and  clavicle,  with 
very  little  loss  of  blood  and  with  all  the  deIit>eration  and  neatness  of  a 
cadaveric  dissection.  (Fig.  2.)  When  this  had  been  done  the  sternomastoid 
was  divided  at  its  sternal  and  clavicular  attachments  and  reflected  outwards, 
thereby  exposing  an  immensely  dilated  jugular  which  completely  overlapped 
and  covered  the  carotid.  (Fig.  4.)  After  dividing  the  omohyoid  and  sterno- 
hyoid, the  site  of  the  anastomosis  was  easily  recognized  as  a  cicatricial 
plug,  which  could  be  felt  over  the  mass  that  bound  the  carotid  and  jugular 
with  the  sheath  of  the  vessels  and  held  them  together  in  an  inextricable, 
fused,  pulsating  mass.  Pressure  at  this  point,  which  was  the  vortex  of  the 
great  circulatory  storm  that  raged  in  these  parts,  put  an  immediate  stop 
to  all  pulsation  and  brought  about  the  collapse  of  the  veins.  We  availed 
ourselves  of  this  subsidence  in  the  venous  swelling  to  clear  out  the  common 
carotid  and  apply  the  aluminum  band  on  this  trunk  at  about  i^  inches 
above  the  left  sternoclavicular  joint.  The  seat  of  the  anastomosis  we  had 
now  located,  with  accurate  precision,  on  a  level  with  the  bifurcation.  On 
releasing  the  pressure  at  this  point,  the  jugular  filled  again  and  pulsated, 
but  very  much  less  vigorously  than  before  the  banding  of  the  carotid.  In 
view  of  this  greatly  diminished  activity  of  the  arteriovenous  circuit,  an 
additional  band  was  placed  on  the  jugular  about  i  inch  from  its  junction 
with  the  subclavian.  Seeing  now  that  the  vein  became  distended  and 
pulsated  to  the  level  of  the  obstruction,  a  chromic  catgut  ligature  was 
placed  on  the  vein  i^  inches  higher  up,  and  that  much  nearer  to  the  anas- 
tomosis. This  reduced  the  size  of  the  ampullar  swelling  very  considerably; 
and,  as  the  first  stage  of  the  operation  had  been  completed,  we  decided  to 
close  the:  wound  provisionally. 

Notwithstanding  the  long  and  tedious  ordeal,  the  patient  was  sent 
back  to  his  bed  in  excellent  condition,  with  a  pulse  of  100,  respirations  22, 
and  in  a  cheerful  frame  of  mind. 

In  the  absence  of  all  complications,  cerebral  or  otherwise,  the  second 
stage  of  the  operation  was  undertaken  on  the  third  day  after  the  first 
operation,  when  the  dressing  was  removed  for  the  first  time. 

Second  stage.  On  lifting  the  cutaneous  flap  the  wound  was  found  clean. 
The  occlusion  of  the  carotid  and  internal  jugular  had  exercised  a  wonderful 


io86     TREATMENT  OF  ARTERIOVENOUS   ANEURYSMS 

influence  in  diminishing  the  venous  turgescence  and  erethism  of  the  whole 
field  of  the  operation.  One  significant  fact  remained — the  arteriovenous 
fistula  at  the  carotid  bifurcation  was  still  active.  The  pulsation  and  thrill 
could  be  still  felt  at  this  point,  though  greatly  subdued.  It  was  evident 
that  the  arteriovenous  fistula  was  now  fed  by  the  arterial  current  which 
was  coming  from  the  collaterals  of  the  opposite  side  through  the  external 
carotid  to  the  internal  carotid  and  again  into  the  jugular  through  the  fistula. 
(See  Fig.  3.)  Evidently,  the  flow  into  the  jugulo-carotid  fistula  could  not  be 
stopped,  or  the  aneurysm  cured,  until  the  circulation  going  on  through  the 
external  and  internal  carotids  had  been  arrested.  To  accomplish  this,  these 
vessels  were  temporarily  and  individually  compressed  above  their  origin  at  the 
bifurcation  with  two  small,  padded  Hoepfner  clamps.  (See  Fig.  3.)  The  inter- 
nal jugular  was  nowligated  on  the  cephalic  side  of  the  arteriovenous  junction. 
This  made  it  safe  to  proceed  with  the  next  step  of  the  operation,  which  was 
to  open  the  jugular  vein  freely  over  the  site  of  the  fistula  and  thus  expose 
the  interior  of  its  ampullar  sweUing  and  close  the  orifice  of  communication 
leading  to  the  artery  through  the  venous  side.  A  longitudinal  incision  of 
about  2  inches  was  made  into  the  venous  pouch  through  its  collapsed 
walls.  The  orifice  of  the  fistula  was  now  brought  to  view.  It  was  elong- 
ated, oval  shaped,  and  half  an  inch  in  its  longest  diameter.  Beyond  it, 
the  lumen  of  the  enlarged  carotid  could  be  recognized,  and  by  passing  a 
vaselined  probe  the  orifices  of  the  internal  and  external  carotids  could  be 
felt  arising  a  short  distance  beyond  the  edge  of  the  opening.  The  opening 
itself  seemed  to  occupy  the  center  of  a  partition  or  diaphragm,  formed  by 
the  adherent  walls  of  the  artery  and  vein.  There  was  no  interposed  space  or 
sac  between  the  two.  The  edges  of  the  fistulous  orifice  were  smooth  and 
rounded,  and  just  thick  enough  to  give  a  good,  firm  grip  to  the  small  curved 
needle  and  paraffined  silk  that  was  used  to  close  it.  Six  continued  sutures, 
passed  through  the  edges  of  the  opening,  were  quite  sufficient  to  close  it 
hermetically.  (See  Fig.  5.)  To  secure  further  protection,  a  second  line  of  con- 
tinued chromic  gut  suture  was  made  to  cover  the  first  line,  by  plicating  the 
relaxed  venous  walls  over  it.  (See  Fig.  6.)  This  reduced  the  cavity  of  the 
venous  sac  to  a  notable  extent,  but  still  left  a  very  considerable  excess  of 
sac,  which  was  partially  trimmed  off  with  scissors — sufficiently  to  permit 
the  complete  obliteration  of  the  cavity  by  infolding  the  edges  of  the  vein 
and  holding  them  in  apposition  ("capitonnage")  by  a  continued  gut  sut- 
ure. In  this  way  what  was  once  a  large  venous  ampulla  was  transformed 
into  a  thick  padded  cord  which  completely  obliterated  the  jugular  from 
the  proximal  to  the  distal  ligatures  which  had  been  previously  placed  on 
the  vein,  above  and  below  the  anastomosis.  (See  Fig.  7.)  The  clamps  were 
now  removed  from  the  external  and  internal  carotids.  It  was  soon  de- 


TREATMENT  OF  ARTERIOVENOUS  ANEURYSMS      1087 

termined  that  a  reduced  circulation  had  been  established  through  these 
vessels,  by  way  of  the  bifurcation,  and  that  while  the  arteriovenous  com- 
munication had  been  completely  closed,  a  new  channel  for  the  arterial 
supply  of  the  brain  had  remained.  In  this  way,  also,  the  main  object  of 
the  operation  had  been  obtained  with  the  sacrifice  of  the  vein,  but  with 
a  greater  conservative  result  on  the  arterial  side  than  we  had  anticipated. 
This  second  sitting  consumed,  in  all,  about  i^  hours,  and  was  also  carried 
out  without  any  general  anesthetic,  except  a  preliminary  hypodermic  of 
morphia  and  scopolamin.  At  the  close,  the  wound  was  carefully  dressed 
and  drained  at  the  lower  angle. 

All  signs  of  the  arteriovenous  anastomosis  had  disappeared  completely. 
From  May  6th  to  8th  the  patient  continued  to  do  well,  only  complaining  of 
pain  in  swallowing.  On  dressing  the  wound  on  the  8th,  evidences  of  suppura- 
tion and  staphylococcal  infection  were  discovered  in  the  tract  of  the  drain, 
and  several  sutures  were  removed,  allowing  some  seropurulent  fluid  to  es- 
cape. The  infection  had  begun  under  the  flap,  and  a  cellulitis  was  suspected 
between  the  lower  carotid  sheath  and  the  pharynx.  The  pulse  rose  to  100° 
and  showed  more  irregularity  and  intermittency.  The  mental  attitude  was 
perfectly  clear  and  even  cheerful;  no  evidences  of  cerebral  disturbances. 
Dysphagia  and  occasional  spells  of  dyspnea  were  the  chief  troubles. 
The  wound  was  dressed  twice  daily,  and  the  infection  seemed  to  be  con- 
trolled. On  the  night  of  the  i  ith  he  became  restless  and  anxious,  and  com- 
plained that  he  could  not  breathe  comfortably  and  had  to  be  propped  up 
on  pillows.  On  the  morning  of  the  12th  he  washed  his  mouth  and  attended 
to  his  toilet  as  usual,  but  persisted  in  sitting  up.  At  8.30  a.m.  he  complained 
of  stenocardiac  pains  and  distress  in  the  precordia,  and  began  to  struggle 
for  breath.  The  pulse  now  became  very  irregular  and  feeble  and  he  expired 
suddenly  before  the  interne  of  the  service  could  reach  him. 

Death,  therefore,  occurred  nine  days  after  the  first  operation,  when  the 
carotid  and  jugular  were  occluded,  and  on  the  sixth  day  after  the  second 
sitting,  when  the  arteriovenous  fistula  was  obliterated. 

At  the  autopsy,  nothing  was  found  in  the  wound  that  could  account  for 
the  fatal  termination.  The  fistula  had  been  completely  sealed  and  all  the 
sutures  had  held.  The  internal  and  external  carotids  were  pervious  and 
free  from  clot.  The  brain  and  thoracic  organs  were  preserved  for  a  separate 
and  detailed  examination  in  the  laboratory.  Marked  evidence  of  chronic 
endarteritis  and  miliary  aneurysms  were  discovered  in  the  cerebral  vessels, 
but  the  cause  of  the  fatal  termination  was  found  in  the  heart.  The  aorta 
was  dilated  and  showed  atheromatous  plaques.  The  left  coronary  was 
obstructed  by  thrombus  and  the  right  ventricle  was  distended  with  clot 
which  extended  into  the  pulmonary  artery.  The  heart  itself  was  of  large 
size,  dilated,  showing  evidence  of  myocardial  degeneration. 


io88     TREATMENT  OF  ARTERIOVENOUS  ANEURYSMS 

I  have  dwelt  with  some  detail  upon  the  ref)ort  of  this  patient's 
case,  because  it  presents  many  unusual,  if  not  unique,  features: 

I.  It  is  the  first  case  that  I  have  been  able  to  discover  in  the 
literature  in  which  the  special  technic  of  transvenous  endoaneurys- 
moraphy  has  been  applied  to  suppress  an  arteriovenous  fistula  of 
the  jugulo-carotid  yessels,  with  technical  success.  The  only  other 
instances  in  which  the  transvenous  method  of  endoaneurysmal  suture 
has  been  apphed  are  reported  six  years  later,  and  are:  (i)  the  opera- 
tion performed  on  a  young  soldier  by  Rene  Le  Fort,  of  Lille,  on 
July  20,  191 7*  in  which  the  internal  carotid  and  jugular  veins  were 
involved.  The  fistulous  communication  was  closed  by  suture,  apphed 
through  an  incision  made  in  the  pouch  formed  by  the  dilated  internal 
jugular.  The  artery  remained  pervious,  and  the  vein  was  obhterated 
by  pHcation  and  mattress  sutures  ("capitonnage"),  as  in  my  case. 
The  wound  had  been  inflicted  four  months  previously,  and  the 
technic  was  remarkable  for  its  simplicity  and  brilhant  success. 

(2)  The  op>eration  reported  by  C.  P.  Lecene  of  Paris'  was  performed 
on  November  15,  191 7.  The  patient,  a  soldier,  aged  twenty-five 
years,  was  wounded  in  the  neck  by  a  fragment  of  shell  which  per- 
forated  the  common  carotid  and  jugular,  causing  an  arteriovenous 
anastomosis.  The  operation  was  performed  about  one  month  after 
the  injury.  In  this,  as  in  my  case  and  Le  Fort's,  the  jugular  vein 
was  enormously  dilated  on  a  level  with  the  arterial  communication. 
The  operator  was  able  to  close  the  slit-hke  opening  of  the  fistula, 
which  was  clearly  visible  inside  of  the  vein,  by  an  intravenous  suture 
with  fine  silk,  and,  in  this  way,  he  did  a  perfect  restorative  endoaneu- 
rysmoraphy,  which  allowed  the  common  carotid  to  remain  pervious. 
The  vein  itself  was  closed  by  intravenous  sutures  apphed  above  and 
below  the  seat  of  the  anastomosis.  The  result  was  a  brilHant  success, 
by  which  the  carotid  circulation  was  restored,  though  the  vein  was 
partially  obhterated. 

This  case,  as  the  preceding  of  Le  Fort,  is  noteworthy  in  many 
ways,  and  especially  as  illustrating  the  relative  facihty  with  which 
the  cure  of  an  aneurysmal  varix  was  effected  in  a  particularly 
dangerous  and  difficult  region.  It  is  also  a  valuable  tribute  to  the 
efficiency  of  the  method,  coming,  as  it  does,  from  an  operator  who 

*  Bull.  Acad,  de  Med.,  Par.,  No.  31,  August  7,  191 7. 

*  Bull,  et  mem.  Soc.  de  cbir.  de  Par.,  January  15,  1918;  XLIV,  No.  i,  27-30. 


TREATMENT  OF  ARTERIOVENOUS  ANEURYSMS      1089 

had  previously  entertained,  and  expressed,  a  decided  prejudice 
against  the  endoaneurysmal  methods  of  suture,  but  who,  after  this 
experience,  loyally  and  honestly  admitted  that  he  had  erred  in  his 
preconceived  objections. 

"Mais  I'experience  qui  seule  juge  en  dernier  ressort,  m*a  montre 
que  mes  preventions  contre  cette  intervention  (I'operation  de  Matas) 
etaient  tout  a  fait  injustifiees." 

2.  In  our  case  the  continuity  of  the  collateral  arterial  current  to 
the  brain  through  the  external  and  internal  carotids  by  way  of  the 
bifurcation  remained  undisturbed,  and  is  also  one  of  the  unique 
features  of  this  case.  The  proof  that  this  collateral  circuit  remained 
active  was  demonstrated  after  the  common  carotid  and  internal 
jugular  had  been  occluded. 

3.  The  chief  indication  for  the  operation  was  also  unusual,  and 
perhaps  unique,  in  the  fact  that  it  was  undertaken  chiefly  with  the 
hope  that  the  closure  of  the  arteriovenous  fistula  would  relieve  the 
strain  on  the  right  heart  caused  by  the  short-circuiting  of  the  carotid 
stream  into  the  venous  system,  causing  a  progressive  dilatation,  with 
dangerous  and  distressing  symptoms. 

The  opportunity  to  test  the  full  value  and  end  results  of  the 
transvenous  route  in  attacking  aneurysmal  varices,  which  was  de- 
nied us  in  the  preceding  case,  soon  presented  itself  in  a  succession 
of  aneurysmal  varices  of  the  lower  extremities,  which  came  under 
treatment  in  our  cHnics  in  the  interval  between  19 12  and  19 19.  The 
following  two  cases,  abstracted  from  our  records,  suffice  to  show 
some  of  the  pecuHarities  of  the  technic,  which  has  varied  according 
to  the  conditions  found  in  each  case,  but  has  always  been  guided 
by  the  same  principle. 

Traumatic  Arteriovenous  Aneurysm  (Aneurysmal  Varix),  Involving  the 
Femoral  Vessels  at  the  Groin,  oj  Three  Years'  Standing  in  which  the  Arterio- 
venous Communication  was  Successfully  Closed  by  Transvenous  Endoan- 
eurysmoraphy,  with  Preservation  oj  the  Lumina  oJ  Both  Vessels.  The 
patient,  J.  H.  H.,  nineteen  years,  of  Westminster,  S.  C,  shot  himself 
accidentally  with  a  parlor  rifle,  .22-caIiber  bullet.  The  buflet  entered  the 
abdominal  wall  about  i^  inches  below  Poupart's  ligament,  and  ranged 
downward,  striking  the  femoral  vessels  at  the  groin,  and  losing  itself  in  the 
depths  of  the  left  thigh.  A  tumor  formed  just  below  the  middle  of  Poupart's 
ligament,  where  a  characteristic  thrill  and  purring  noise  developed  on  the 


1090     TREATMENT  OF  ARTERIOVENOUS   ANEURYSMS 


o^  bullet. 


third  day  following  the  injury.  He  came  under  my  observation  on  January 
II,  1912,  three  years  after  the  accident  occurred.  The  affected  limb  was 
larger  than  the  right,  and  he  had  large  varicosities  all  along  the  saphenous 

tract  from  the  thigh  to  the  leg,  with 
typical  pigmentation  of  the  skin 
and  a  rebellious  ulcer  below  the 
knee  which  had  resisted  all  pre- 
vious treatment.  The  site  of  the 
abnormal  vascular  communication 
was  easily  localized  at  a  point  just 
below  Poupart's  ligament,  a  little 
to  the  inner  side  of  the  mid  line. 
At  this  point,  the  pulsation,  thrill, 
and  characteristic  murmurs  were 
heard  with  greatest  intensity.  From 
this  point  the  murmurs  and  thrill 
were  transmitted  upward  as  far  as 
the  umbilicus  and,  below,  as  far  as 
the  knee.  The  details  of  the  opera- 
tion which  followed  are  well  shown 
in  the  accompanying  diagrams  and 
drawings.  The  iliac  vessels  were 
exposed  by  an  extensive  subperi- 
toneal dissection,  great  difficulty 
being  experienced  in  controlling  the 
external  iliac  vein  and  its  tribu- 
taries, which  had  attained  enor- 
mous proportions.  The  iliac  vessels 
were  provisionally  controlled  above 
and  below  the  anastomosis  (after 
Poupart's  ligament  had  been  divi- 
ded) by  elastic  ligatures  and  pad- 
ded clamps.  The  common  femoral 
veins  formed  a  large,  well-defined 
sac  of  egg-like  shape  at  the  site  of 
the  fistula  at  its  junction  with  the  saphenous.  After  controlling  all  the  ves- 
sels, the  aneurysmal  phenomena  were  all  stilled  and  the  vessels  collapsed. 
The  sac,  which  was  fully  3^  inches  in  length  and  2  inches  in  breadth,  had  de- 
veloped between  the  artery  and  the  vein,  but  at  the  expense  of  the  vein.  The 
constriction  or  neck  which  united  the  sac  with  the  artery  was  fully  i^  inches 
in  length.  The  sac  was  opened  longitudinally  on  the  venous  side,  exposing 


Fig.  8.  Case  of  J.  H.  H.  (Arteriovenous 
Aneurysm    of    the    Common     Femoral 

Vessels) 

Showing  Comparative  Measurements 
OF  the  Lower  Extremities;  Swelling 
Caused  by  Varicosities  and  Edema;  Also 
Ulcer  below  Knee  and  Line  of  Incision, 
and  Scar  Showing  Entrance  of  Bullet. 


TREATMENT  OF  ARTERIOVENOUS  ANEURYSMS      1091 

the  full  length  of  the  large  orifice  in  the  artery.  This  was  closed  by  a  row 
of  continued,  vaselined  silk  sutures  ijitroduced  from  the  venous  side, 
thus  bringing  the  endothelial  surfaces  of  the  orifices  in  perfect  app)osition. 
After  this,  a  cuff  flap  was  cut  off  at  the  expense  of  the  venous  wall,  thus 
detaching  the  artery  completely  from  the  vein.  This  flap  was  sutured  over 
the  cuff  in  the  manner  shown  in  the  diagram,  leaving  the  artery  thoroughly 
protected  against  leakage.  The  suture  of  the  vein  was  easily  accomplished, 
owing  to  the  excess  and  laxity  of  the  venous  sac.  After  this,  aU  the  con- 
trofling  elastic  ligatures  and  clamps  were  removed,  allowing  the  blood 
stream  to  return  at  once  through  its  normal  channel.  All  the  sutures  in  the 
artery  and  vein  held  perfectly,  insuring  the  complete  success  of  the  opera- 
tion. The  operation  was  long  and  tedious,  as  was  to  be  expected  in  such  a 
chronic  case,  lasting  nearly  four  hours.  This  was  due  chiefly  to  the  innumer- 
able and  enormously  dilated  veins  which  had  to  be  secured  and  extirpated 
in  the  superficial  planes  before  the  main  vessels  could  be  reached.  (See 
Figs.  9-16). 

The  most  notable  post-operative  feature  of  the  case  was  the  extraor- 
dinary tachycardia  that  developed  suddenly  after  the  restoration  of  the 
circulation  through  its  normal  channels.  This  tachycardia,  during  which 
the  pulse  ranged  from  170  to  190,  continued  until  after  the  patient 
had  recovered  from  the  anesthesia,  and  lasted  for  three  hours  after  he  was 
returned  to  his  bed.  At  the  end  of  this  time  the  pulse  suddenly  became 
irregular  and  dropped  in  three  minutes  to  no,  where  it  continued  until  it 
became  normal  the  next  day.  Apart  from  this  remarkable  incident  the 
patient  made  an  excellent  recovery  and  was  discharged  completely  healed 
and  well,  on  February  19,  191 2.  Three  years  after  his  return  home  his 
physician  wrote  me  that  the  boy  had  been  in  perfect  health  and  that  he 
had  grown  to  be  a  big  and  robust  man. 

In  this  case,  as  in  all  others  of  long  standing,  the  baneful  effects 
of  the  short-circuiting  of  the  large  arterial  channels,  into  the  ven- 
ous circulation,  especially  at  the  root  of  the  limbs,  were  particularly 
noticeable,  showing  that  the  sudden  readjustment  of  the  circulation 
by  the  closure  of  the  abnormal  arteriovenous  communication  is  not 
without  its  dangers. 

Arteriovenous  Aneurysm  of  the  Femoral  Vessels  at  the  Apex  of  Scarpa*s 
Triangle  in  a  Boy  of  Fifteen  Years  in  wbicb  the  Orifice  oj  Communication 
wcLS  Closed  by  a  Trans-arterial  Suture.  A  pulsating  hematoma  caused  by 
the  simultaneous  transfixion  of  the  artery  and  puncture  of  the  vein  by  stab. 
(See  Fig.  17.)  This  boy,  J.  B.,  was  brought  to  me  from  Sterling  City,  Texas, 


1092      TREATMENT  OF  ARTERIOVENOUS  ANEURYSMS 


September  3,  1916,  twenty-four  days  after  he  had  accidentally  wounded 
himself  in  the  right  thigh  with  a  long-bladed  pocket  knife,  while  splitting 
a  piece  of  wood.  The  knife  had  entered  the  upper  thigh  about  5  inches  be- 
low Poupart's  ligament.  The  boy  was  still  suffering  from  the  effects  of 
severe  hemorrhage.  A  linear  scar  indicated  the  point  of  entrance  of  the 
knife,  and  about  this  was  a  spherical  swelling  which  pulsated,  purred,  and 
thrilled  in  the  characteristic  fashion  of  arteriovenous  injuries.  The  pedal 
pulses  were  feeble,  but,  on  testing  the  collateral  circulation  by  our  methods, 

it  was  shown  that  an  ample  supply  of 
blood  was  going  to  the  periphery  by  the 
collaterals  outside  of  the  main  channels, 
and  that  an  obliterative  operation  could 
be  performed  with  safety,  if  it  became 
necessary.  Prophylactic  hemostasis  was 
secured  by  the  Esmarch  bandage,  and 
the  constrictor  was  held  high  up  near  the 
groin  with  a  Wyeth  pin.  With  the  scar  as 
the  center  of  the  incision,  a  sac  was 
opened  above  the  sartorius,  which  led  to 
another  cavity  under  this  muscle.  This 
cavity  was  already  partially  lined  with 
a  thin  veil  of  organized  exudates  which 
hid  the  vessels  completely.  A  slit-Iike 
opening  about  half  an  inch  in  length  was 
now  discovered  in  the  floor  of  this  space, 
running  parallel  with  the  long  axis  of 
the  femoral  vessels,  which  were  lying 
superimposed  one  on  the  other  under  the 
thin  lining  of  the  sac.  An  exploration  of 
this  opening  with  a  probe  demonstrated 
that  it  led  to  the  artery  and  not  the  vein,  as  we  had  at  first  supposed,  and 
that  this  vessel  had  been  transfixed  and  the  vein  punctured. 

The  flatness  and  breadth,  as  well  as  thinness  of  the  collapsed  artery, 
with  the  narrow  slit-Iike  wound  lying  in  its  center,  permitted  us  to  suture 
and  obliterate  the  arteriovenous  opening  simultaneously  with  the  external 
wound  in  the  artery.  The  technic  adopted  is  shown  in  the  accompanying 
Figs.  18  and  19.  On  removal  of  the  constrictor  the  blood  rushed  into  the  ar- 
tery, which  pulsated,  circulating  on  each  side  of  the  suture  line,  and  be- 
yond, into  the  artery,  distal  to  the  central  line  of  suture.  All  the  aneurys- 
mal signs  ceased  completely  and  the  circulation  of  the  foot  was  perfect,  the 
pedal  pulses  remaining  as  they  had  been  before  the  operation.  Healing  took 


Fig.  17.  Case  of  J.  B.  (Arterio- 
venous Hematoma  of  femoral  ves- 
sels.) a.  Shows  How  Penetration  of 
Both  Vessels  was  Made  with  Pen- 
knife; h.  Portion  of  Scar  where  Thrill 
and  Other  Aneurysmal  Signs  were 
Most  Marked;  also  Prophylactic 
Hemostasis  with  Constrictmg  Elas- 
tic Band  Held  in  Place  by  Wyeth  Pin. 


TREATMENT  OF  ARTERIOVENOUS  ANEURYSMS      1093 

place  per  primam,  and,  after  a  short  period  of  rest,  hydrotherapy,  and 
massage  the  patient  was  discharged,  healed  and  well,  on  the  twentieth  day 
after  the  operation.  I  have  since  frequently  heard  from  the  patient,  and  up 
to  the  present  time  he  is  in  perfect  health. 

This  operation  is  unusual  and  perhaps  unique  in  the  fact  that  an 
arteriovenous  fistula  was  obliterated  through  an  abnormally  thin  arterial 
wall,  thus  constituting  a  trans-arterio-phleboraphy  rather  than  the  usual 
procedure  of  trans-phlebo-arterioraphy. 

Our  records  show  that  four  additional  cases  of  arteriovenous  an- 
eurysms involving  the  femoral  vessels  have  been  operated  upon  in  our 
clinics  since  going  through  the  preceding  experiences,  which  exhibit 
individual  features  and  peculiarities  of  special  interest  to  the  surgical 
technician  that  deserve  detailed  consideration  in  a  separate  publica- 
tion. They  all  have  the  one  feature  in  common,  in  that  they  were 
long-standing  aneurysmal  varices  presenting  all  the  difficulties  and 
complications  peculiar  to  the  chronic  stages  of  this  class  of  lesions, 
each  one  offering  a  serious  problem  to  tax  the  judgment,  skill,  and 
resourcefulness  of  the  most  experienced  operator.  All  of  these,  how- 
ever, were  happily  solved  by  the  intrasaccular  and  transvenous 
methods  herein  described,  with  such  modifications  as  were  suggested 
by  the  conditions  met  in  the  course  of  the  operation.  Finally,  the 
experience  gathered  from  these  cases  has  convinced  me  that  the  pos- 
sibilities of  cure  by  this  method  are  as  great  in  arteriovenous  aneu- 
rysms as  in  the  purely  arterial. 

BIBLIOGRAPHY— SIR  WM.  OSLER'S  WRITINGS  ON  ANEURYSM 

[Perhaps  no  better  illustration  of  Sir  William  Osier's  broad  catholicity  of  spirit 
and  profound  interest  in  every  influence  that  tends  to  the  uplift  of  medicine  in  all  its 
relations,  could  be  offered,  than  in  his  keen  appreciation  and  penetrating  insight  into 
the  borderland  problems  of  vascular  surgery.  His  numerous  contributions  to  the  knowl- 
edge and  literature  of  vascular  diseases,  and  especially  aneurysm,  even  to  the  most 
surgical  of  these,  arteriovenous  injuries  (incompletely  represented  in  this  bibliography), 
reveal  the  same  accuracy  of  observation,  the  same  capacity  to  collect,  analyze,  and 
interpret  facts,  the  far-reaching  clearness  of  the  philosopher  and  erudite  scholar  that 
characterize  all  his  writings  in  every  department  of  thought  which  he  has  touched  with 
the  magic  of  his  pen  and  illumined  with  his  genius. — R.  M.] 

Geo.  Ross  and  W.  Osier,  "Case  of  Aneurysm  of  the  Hepatic  Artery  with 
Multiple  Abscesses  of  the  Liver,"  Canad.  J.  M.erS.,  1877-78,  VI,  i. 

W.  Osier,  "Case  of  Arteriovenous  Aneurysm  of  the  Axillary  Artery  and 
Vein  of  Fourteen  Years'  Duration,"  Ann.  Surg.,  1893,  XVII,  37. 


1094     TREATMENT  OF  ARTERIOVENOUS   ANEURYSMS 

W.  Osier,  "Notes  on  Aneurysm,"  J.  Am.  M.  Ass.,  1902,  XXXVIII,  1483. 
W.  Osier,  "Aneurysm  of  the  Descending  Thoracic  Aorta,"  Internal.  Clin., 

1903,  Sen  XIII,  Vol.  I,  p.  i. 
W.  Osier,  "Aneurysm  of  the  Arch  of  the  Aorta  and  Innominate,"  Johns 

Hopkins  Hosp.  Bull.,  1904,  XV,  66. 
W.  Osier,  "Aneurysm  of  the  Abdominal  Aorta,"  Lancet,  October  14,  1905, 

II,  1089. 
W.  Osier,  "Angina  Pectoris,  as  an  Early  Symptom  in  Aneurysm  of  the 

Aorta,"  Med.  Cbron.,  May,  1906,  XI,  69. 
W.  Osier,  "Aneurysm,"  in  Clifford  Allbutt  and  Humphry  Davy  RoIIes- 

ton's  "System  of  Medicine  by  Many  Writers,"  VI;  "Diseases  of 

the  Heart  and  Blood  Vessels,"  1909,  620-681. 
W.  Osier,  "Aneurysms":  "Aneurysm  of  the  Thoracic  Aorta;  Aneurysm  of 

Abdominal  Aorta;  Aneurysm  of  the  Branches  of  the  Abdominal 

Aorta;  Arteriovenous  Aneurysms — ^Aneurysmal  Varix."  Section  IX, 

"Diseases   of  the  Circulatory  System,"   in   "The   Principles   and 

Practice  of  Medicine,"  Eighth  Edition,  1916,  847-861. 
W.  Osier,   "Remarks  on  Arteriovenous  Aneurysm."   (Symposium  on  the 

subject  at  Radcliffe  Infirmary,  Oxford,  March  26,   1915.)  Lancet, 

London,  May  8,  19 15. 


EXSTROPHY  OF  THE   BLADDER 
By  C  H.  Mayo,  M.D.,  Rochester,  Minn. 

OF  the  many  human  defects  none  is  more  serious  or  trouble- 
some to  contend  with  than  the  condition  of  exstrophy  of 
the  bladder.  It  occurs,  according  to  Spooner,  four  times  in 
1 16,000  births;  according  to  Neudorfer  once  in  50,000  births,  and  since 
1896  it  has  been  observed  in  52  instances  in  the  routine  examination 
of  patients  in  the  Mayo  Clinic.  The  reason  for  the  occurrence  of  this 
as  well  as  of  other  anomalies  has  not  as  yet  been  satisfactorily 
explained.  It  has  been  shown  experimentally,  however,  that  defects 
of  development  may  follow  changes  in  the  salts  of  the  fluid  which 
surrounds  the  developing  egg. 

The  seriousness  of  the  condition  of  exstrophy  of  the  bladder 
hardly  needs  to  be  commented  on.  Statistics  show  that  50  per  cent 
of  all  persons  thus  afflicted  are  dead  by  their  tenth  year,  and  66.67 
per  cent  are  dead  by  their  twentieth  year.  Other  defects  are  often 
associated  with  it,  such  as  hydrocephalus,  spina  bifida,  hare-lip, 
imperforate  or  paretic  anus,  with  rectal  prolapse,  and  epispadias, 
which  is  usually  present  in  the  male,  in  whom  80  per  cent  of  these 
cases  are  found.  In  the  female  the  clitoris  and  labium  minora  are 
divided.  In  all  cases  the  pubic  arch  is  incomplete  anteriorly,  and 
separated  for  from  2  to  4  inches.  Hernia,  congenital  or  acquired, 
of  one  or  both  sides,  is  often  an  accompanying  defect,  and  occasion- 
ally an  umbiHcal  protrusion  is  seen  adjoining  the  upper  margin  of 
the  bladder.  The  pelvis  is  broader  and  flatter  than  normal,  a  de- 
formity which  turns  the  femurs  outward  and  produces,  in  extreme 
conditions,  a  curious  wabbling  gait.  The  umbiHcus  is  situated  lower 
on  the  abdomen  than  is  usual;  it  is  scarcely  noticeable  as  it  joins 
the  upper  bladder  mucosa,  thus  showing  that  the  defect  occurs  at 
the  early  period  when  the  allantois  is  present.  As  there  is  no  urachus 
the  separation  may  extend  from  the  cord  juncture  to  the  terminus 
of  the  urethra.  Cases  have  been  reported  in  which  a  normal  urethra 
was  present;  this  makes  it  improbable  that  obstruction  and  rupture 
could  be  a  causative  factor  in  its  production  (Duncan,  1805).  The 

1095 


1096  EXSTROPHY  OF  THE  BLADDER 

period  of  development  probably  occurs  when  the  pubic  bone  is 
still  separated;  one  case  is  reported,  however,  of  a  child  of  five 
years  with  exstrophy  of  the  bladder,  the  result  of  an  assault,  in 
which  the  pubic  bones,  originally  joined,  were  later  absorbed.  The 
exposure  and  irritation  of  the  bladder  surface  and  the  odor  of  leaking 
urine  from  the  saturated  absorbent  cloths  produce  a  most  distressing 
condition,  and  lead  persons  thus  affected  to  shun  society;  in  fact 
unless  an  early  operation  is  done,  very  few  will  have  school  ad- 
vantages (Fig.    i). 

Procreation  in  the  male  with  this  defect  has  not  been  reported. 
Winslow  in  1906  reported  one  case  of  a  woman  who  had  borne  four 
children,  and  Moorhead  in  191 6  reported  one  case  of  a  woman  who 
had  borne  two  children.  One  of  our  patients,  operated  on  by  the 
plastic  method,  died  later  in  childbirth;  the  baby  weighed  i2i/^ 
pounds.  In  the  females  with  this  defect  whom  we  have  seen,  the 
vagina,  uterus,  ovaries,  and  tubes  were  normal,  except  in  one  case 
of  bifid  uterus  and  double  vagina. 

Deaths  incident  to  the  anomaly  are  usually  due  to  nephritis, 
which  may  occur  early  from  infection,  or  following  a  contracture 
of  the  lower  ends  of  the  ureter  because  of  thickening  of  the  bladder 
wall,  which  causes  hydro-ureter  and  hydro-nephrosis.  Later  this 
becomes  a  pyonephrosis,  but  the  infection  does  not  necessarily 
travel  through  the  lymphatic  system  of  the  ureter,  as  noted  by  Sweet 
and  Stewart. 

The  difficulties  of  developing  control  of  the  urine  in  a  receptacle 
formed  from  the  remaining  bladder  tissue  were  early  appreciated 
by  scientific  investigators.  With  the  idea  of  bringing  about  a  cloacal 
condition  as  common  to  birds,  the  ureters  were  transplanted  into 
the  intestine.  This  was  first  done  unsuccessfully  in  1851  by  Simon. 
In  1852  Roux  developed  special  plastic  procedures  for  the  formation 
of  a  bladder,  and  in  later  years  various  additions  and  changes  in  the 
plastic  method  were  devised  by  Nelaton  (1854),  Thiersch  (1876), 
Wood  (1880),  and  others,  and  more  recently  (191 7)  by  Kanavel, 
who  transplanted  protective  fascial  layers  to  cover  the  closed  wall 
of  the  bladder.  The  great  objection  to  the  plastic  closure  methods  is 
the  necessity  of  using  adjacent  hair-growing  skin,  which  later  ac- 
cumulates lime  deposits  and  adds  to  the  foulness  of  the  uncontrolled 
bladder. 


EXSTROPHY  OF  THE  BLADDER  1097 

In  1 88 1  Gluck  and  Zeller  made  experimental  animal  transplants 
of  the  ureter  to  the  intestine;  the  method  gave  a  high  mortahty. 
Trendelenburg  in  1885,  followed  by  Passavant  in  1887,  aided  closure 
and  bladder  formation  by  compressing  the  half-formed  pubic 
arches.  Konig  in  1896,  Koch  in  1897,  and  others,  made  subcutaneous 
section  of  the  bony  arches  to  aid  in  the  development  of  the  bladder. 
In  1892  Trendelenburg  reported  his  addition  to  the  method,  that  of 
separating  the  sacro-iliac  joints.  This  method  was  also  used  by 
Albarran  in  1909.  Such  procedures  were  of  a  serious  nature,  and  a 
20  per  cent  surgical  mortality  followed  the  formation  of  the  uncon- 
trolled bladder  pouch,  which  left  the  patient  in  greater  danger  of 
subsequent  renal  infection. 

In  1878  Thomas  Smith,  returning  to  cloacal  methods,  trans- 
planted both  ureters  into  the  rectum,  extraperitoneally,  and  in  1891 
Kuester  performed  the  same  operation  following  removal  of  the 
bladder  for  cancer.  In  both  instances  the  results  were  fatal.  The 
first  successful  bilateral  transplantation  of  the  ureters  after  opera- 
tion for  cancer  was  that  by  Chalot  in  1896.  Chaput  in  1892  had 
transplanted  one  ureter  into  the  rectum  for  the  cure  of  ureterovaginal 
fistula.  The  patient  hved  nine  years,  having  three  liquid  stools  a 
day.  This  case  was  reported  as  the  first  success  of  unilateral  trans- 
plantation. The  other  kidney  and  the  other  ureter  and  the  bladder 
were  intact.  Also  in  1896,  Maydl  transplanted,  intraperitoneally, 
the  base  of  the  inverted  bladder  with  the  attached  ureters  into  the 
sigmoid;  this  became  the  popular  operation.  Orlow  in  1904,  in  a 
study  of  56  such  cases,  showed  that  4  of  1 1  deaths  were  due  to 
peritonitis.  He  reported  a  mortahty  of  17  per  cent  in  61  cases. 
Other  Russian  surgeons  reported  a  mortahty  of  32  per  cent,  while 
Drucbert  (1904)  reported  27  per  cent  in  81  cases.  Moorhead  in 
19 1 6  collected  154  cases  in  which  an  early  mortahty  of  28.5  per 
cent  was  shown.  Two  of  three  of  our  patients  operated  on  by  this 
method  died.  A  change  in  the  technic  had  been  attempted  by  Ber- 
genhem  in  1894.  He  transplanted  the  ureters  into  the  rectum 
extraperitoneally,  but  he  was  not  accorded  the  recognition  for  the 
operation  that  Lendon  and  Peters  received,  who  performed  it  in 
May  and  in  July,  1899,  respectively. 

Jaja  in  1901  performed  the  operation  intraperitoneally,  Sherman 
in  1905  dissected  the  ureters  to  preserve  their  mucous-covered  small 


lopS  EXSTROPHY  OF  THE  BLADDER 

exits,  while  Knaggs  in  1908  operated  through  the  Kraske  incision 
and  attached  the  ureters  to  the  rectum,  where  they  came  in  contact 
with  it  laterally. 

Worthy  of  mention,  from  an  historical  standpoint,  are  those 
operations  which  united  the  early  closed  small  bladder  to  the  rec- 
tum, or  which  formed  a  ureterorectal  fistula.  This  anastomosis  was 
secured  by  means  of  a  necrosis  caused  by  tight  sutures,  spring 
forceps,  or  the  Boari  spring  button.  This  type  of  operation  was 
recommended  by  Lloyd  and  by  Johnson  in  1851,  and  by  Simon  in 
1852. 

Valve  types  of  operation  were  performed  by  Fowler  in  1898, 
by  Martin,  and  by  Carl  Beck  in  1899,  and  by  Frank  in  1901.  In 
the  80  cases  collected  by  Buchanan  (1909)  there  was  a  28.7  per 
cent  mortality,  practically  the  same  as  from  the  Maydl  operation, 
and  without  the  danger  of  peritonitis,  as  they  were  extraperitoneal. 

Moynihan  in  1906  changed  the  Maydl  operation  to  an  extraperi- 
toneal one  by  uniting  a  very  much  larger  inverted  section  of  the 
bladder  into  an  opening  in  the  anterior  wall  of  the  rectum.  Since  80 
per  cent  of  these  cases  occur  in  males,  the  operation  is  not  difficult, 
and  the  pouch  connected  with  the  rectum  is  more  Hke  a  true  cloaca. 

Rutkowski  in  1898  used  successfully  an  isolated  segment  of  the 
small  bowel  to  cover  in  the  defective  bladder. 

Werelius  in  1911  developed  methods  of  partially  excluding  the 
segment  of  bowel  to  which  the  ureters  were  united  by  a  high  division 
of  the  sigmoid  with  side-to-side  union  of  the  proximal  end  with  the 
upper  rectum  to  re-establish  the  bowel  continuity,  and  later  the 
ureters  were  united  separately,  or  by  the  Maydl  method,  to  the 
blind  end  of  the  sigmoid. 

Nature's  method  of  emptying  a  duct  is  always  by  indirection, 
thus  the  salivary  ducts,  the  common  duct  of  the  liver,  and  the  ure- 
ters pass  through  the  muscularis  and  continue  for  a  distance  between 
the  mucous  membrane  and  the  firmer  outer  wall  of  the  cavity. 
Pressure  from  within  compresses  the  ducts  and  blocks  against  dila- 
tation and  ascending  infection.  Coffey  has  shown  that  the  common 
duct  is  thus  protected  for  from  2  to  3  cm.  Cabot  shows  a  similar 
condition  in  the  ureterovesical  entrance.  Petit  had  called  attention 
to  this  fact  in  1 790.  The  internal  pressure  of  the  contents  of  the  bowel 
by  gases  or  liquids  compresses  the  duct  in  the  wall  according  to  the 


EXSTROPHY  OF  THE  BLADDER  1099 

tension  within  the  intestine  and  yet  does  not  interfere  with  the  peri- 
staltic delivery  of  its  contents.  The  fact  seemingly  was  not  recognized 
that  the  mechanical  principle  of  the  passage  of  the  ureter  through 
the  wall  of  the  bladder  and  its  mucosa  could  not  be  retained  after 
the  loss  of  its  innervation.  The  Maydl  or  the  Moynihan  operation 
would  be  ideal  could  the  innervation  of  the  bladder  wall  be  retained. 
In  fact  this  jvas  proved  by  Keen's  case  of  vesicovaginal  rectal  fistula. 
The  patient  was  cured  by  the  closing  of  the  vaginal  entrance  and  was 
reported  well  with  the  cloacal  condition  twenty-two  years  later. 

Those  who  beheved  in  developing  a  bladder  out  of  the  remaining 
bladder  tissue  were  not  idle  during  this  time.  Subbotin  in  1901  and 
Diakonow  in  1908  separated  a  strip  of  the  bladder  wall,  shaped  it 
into  a  tube,  and  drew  it  through  the  space  tunneled  between  the 
sphincter  ani  and  the  rectal  mucosa;  the  anal  sphincter  closed  the 
new  urethra  as  well  as  the  anus.  Lerda  in  191 3  modified  this  opera- 
tion by  using  Thiersch  grafts  and  skin  for  the  tube.  The  operative 
mortality  in  these  cases  was  25  per  cent  and  the  bladder  still  re- 
mained a  septic  sac;  apparently  the  better  the  control  the  greater 
the  danger.  The  next  eff"ort  was  to  make  a  new  bladder  from  a  sepa- 
rated loop  of  intestine.  Gersuny  in  1898,  and  Cuneo  in  191 2  separated 
a  loop  of  ileum,  and  after  re-establishing  the  continuity  of  the  intes- 
tine, brought  one  end  of  the  loop  down  through  a  tunnel  made 
within  the  anal  ring,  but  outside  of  the  rectal  mucosa,  and  at  a  second 
operation  transplanted,  intraperitoneally,  the  base  of  the  bladder 
into  the  upper  end  of  the  short  segment  of  bowel.  The  Heitz-Boyer 
and  Hovelacque  operation  (191 2)  converted  the  rectum  into  the 
bladder  by  dividing  the  rectosigmoid,  closing  the  distal  division, 
and  drawing  the  divided  sigmoid  through  a  tunnel  made  by  sepa- 
rating the  anal  mucosa  from  within  its  sphincter.  The  ureters  were 
united  with  the  rectum  extraperitoneally  or  by  Moynihan's  method. 
The  mobilized  bowel  is  large;  it  interferes  with  innervation,  and 
frequently  the  anal  control  is  none  too  good;  in  fact,  infants  with 
exstrophy  often  have  prolapse  as  an  associated  defect.  This  method 
was  ingenious,  but  impracticable,  since  it  was  impossible  to  keep  fecal 
infection  from  contaminating  the  new  bladder. 

Verhoogen  in  1908  suggested  still  another  method  of  forming  a 
closed  urinary  bladder  from  a  segment  of  intestine.  The  operation 
was  made  by  dividing  the  ascending  colon  and  the  ileum  near  the 


1 100  EXSTROPHY  OF  THE  BLADDER 

ileocecal  valve;  the  four  ends  were  closed  and  the  intestinal  canal 
completed  by  a  side-to-side  union  of  the  ileum  to  the  transverse 
colon.  An  appendicostomy  was  made  by  drawing  the  appendix 
through  a  perforation  in  the  abdominal  wall,  and  a  catheter  was 
passed  through  the  appendix  for  irrigating  the  cecum.  At  a  second 
operation,  when  the  cecum  was  apparently  clean,  the  base  of  the 
bladder  with  the  ureters  were  united  to  the  cecum  by  the  Maydl 
method,  and  the  cecum  was  emptied  of  urine  at  regular  intervals  by 
catheter.  Verhoogen's  first  two  patients,  died.  Makkas  operated 
successfully  by  this  method,  however,  in  19  lo.  I  saw  the  patient  two 
years  afterward,  at  which  time  barium  injection  into  the  cecum 
revealed  great  distention  of  both  ureters,  including  their  terminal 
ends  and  the  pelves  of  the  kidneys,  showing  that  the  Maydl  opera- 
tion with  the  loss  of  innervation  of  the  bladder  wall  does  not  afford 
protection  to  the  ureters  and  pelves  from  intra-intestinal  pressure. 
It  should  be  taken  into  consideration  that  not  only  must  the  urine 
be  eliminated  by  kidney  action,  but  also  it  must  be  excreted  from 
the  body,  instead  of  being  placed  in  an  absorbent  area  of  the  intes- 
tine. Berg  demonstrated  that  when  all  the  urine  traversed  the  length 
of  the  colon  urinary  intoxication  occurred.  Bereznjagowski,  Tichow, 
and  Miratworzeff  recommended  low  attachment  and  frequent 
evacuations  to  prevent  absorption.  The  large  bowel  has  few  lymphat- 
ics, but  it  is,  nevertheless,  a  great  water  absorber,  especially  on  the 
right  side,  and  filters  into  the  veins.  Because  of  the  dangers 
of  nephritis  with  the  usual  transplant  of  ureters  into  the  intestine, 
it  was  thought  by  some  observers  that  if  a  natural  tube  or  duct 
entrance  to  the  intestine  could  be  utilized  in  uniting  the  ureters  to 
the  intestine,  the  element  of  sepsis  would  be  reduced.  The  right  ureter 
was  therefore  passed  into  the  appendix  and  united  there,  and  the 
left  ureter  was  passed  into  the  sigmoid. 

Baird,  Scott,  and  Spencer  in  191 7,  in  experimental  work  on  dogs, 
seeking  to  avoid  the  dangers  of  infection  from  septic  invasion  of  the 
kidney  through  the  lymphatics  of  the  ureter,  as  indicated  by  Sweet 
and  Stewart,  united  one  ureter,  the  right,  with  the  larger  duct  of  the 
pancreas.  In  this  relatively  clean  alkahn  field,  apparently  no  lym- 
phatic involvement  occurred  in  from  seven  to  ten  weeks.  The  re- 
maining kidney  was  removed  and  all  the  dogs  died  within  twelve 
days  from  urinary  intoxication.  This  result  was  anticipated  by  Con- 


EXSTROPHY  OF  THE  BLADDER      .         iioi 

nell's  experiments  in  1901  in  developing  a  bladder  from  closed  loops 
of  small  intestine;  the  animals  survived  the  first  ureteral  attachment 
and  died  at  the  second. 

Every  case  of  exstrophy  of  the  bladder,  or  every  case  in  which  it  is 
necessary  to  remove  the  bladder,  must  be  considered,  from  the 
standpoint  of  operation,  on  its  individual  merits.  Such  considerations 
have  to  do  with  the  age,  the  general  condition  of  the  patient,  the 
functional  activity  of  the  ureters  and  kidneys,  and  in  some  cases, 
as  was  recommended  by  Edmunds  and  Ballance  in  1886,  we  must 
be  content  with  the  deliverance  of  urine  to  the  skin  surface  and  the 
reliance  on  some  collecting  retention  apparatus  to  care  for  the  urine. 
The  greatest  dangers  are  apparently  those  of  partial  obstruction, 
causing  hydronephrosis  and  hydro-ureter,  which  later  may  destroy 
the  kidney  by  infection  or  cystic  degeneration.  Watson's  method  of 
nephrostomy  has  proved  satisfactory.  He  reported  three  cases;  one 
patient  was  living  after  sixteen  years  with  tube  drainage  into  the 
back.  I  have  had  one  patient,  a  man  of  forty-five,  in  whom  the 
bladder  was  removed  for  cancer  and  both  ureters  brought  into  the 
back,  who  is  well  after  nearly  ten  years.  The  urine  is  collected  by 
cup  disks  and  carried  by  tubes  into  a  urinal. 

It  has  been  recommended,  under  certain  conditions  of  removal  of 
the  bladder  for  exstrophy  with  dilated  ureters,  to  bring  the  ureters 
through  lateral  punctures  made  in  the  abdominal  wall,  and  to 
control  the  urine  by  collectors  held  with  an  abdominal  belt.  Bovee 
collected  ten  such  reported  cases.  The  operation  has  been  rep)orted 
by  Bottomley,  Rovsing,  Coffey,  and  others. 

Harrison  in  1897  performed  the  operation  on  one  side  and 
destroyed  the  opposite  kidney  by  ligating  its  ureter.  I  used  Sonnen- 
berg's  method  of  removal  of  the  bladder  in  one  case.  After  removing 
the  bladder  for  cancer  I  attached  the  ureters  to  the  proximal  end 
of  the  urethra,  and  the  urine  was  collected  by  a  bulbous  catheter. 
The  patient  died  of  nephritis  during  the  second  year  after  the 
operation.  Pawlick,  Summers,  Chavasse,  and  others  removed  the 
bladder  wall  and  developed  a  ureterovaginal  fistula,  but  as  approx- 
imately only  20  per  cent  of  those  afflicted  with  exstrophy  of  the 
bladder  are  females,  and  this  procedure  accomplishes  only  the 
removal  of  the  bladder  wall,  it  was  not  of  general  applicability. 

I    believe   that   the   most   satisfactory   operation   in   cases    of 


1 102  EXSTROPHY  OF  THE  BLADDER 

exstrophy  of  the  bladder  in  which  the  ureters  are  normal,  or  nearly 
so,  is  uniting  the  ureters  with  the  rectosigmoid  on  the  right  side  and 
to  the  sigmoid  on  the  left  side.  There  are  two  methods  of  accom- 
plishing this,  both  intraperitoneal.  The  older  method  has  been 
used  by  Russian  and  Polish  surgeons,  and  by  Stiles.  These  surgeons 
divided  the  ureter,  isolated  it  from  the  peritoneum  for  some  distance, 
and  passed  it  into  the  bowel  through  a  small  puncture,  where  it  was 
held  by  suture.  The  ureter  was  depressed  into  the  wall  of  the 
intestine  and  the  folds  of  bowel  were  sutured  together  over  it  for  a 
distance  of  i  inch  or  more;  the  operation  is  similar  to  that  known 
as  the  Witzel  method  of  gastrostomy  or  enterostomy,  in  which  a 
rubber  tube  is  used  in  the  same  manner.  The  operation  is  theoretic- 
ally defective  in  that  the  channel  is  made  of  the  entire  thickness  of 
the  intestinal  wall,  and  that  it  is  too  rigid  to  be  controlled  by  the 
internal  pressure.  Such  pressure  is  adequately  secured  by  the  Coffey 
method. 

Tecbnic  of  Operation  for  Exstrophy  of  the  Bladder  as  Performed  in 
the  Mayo  Clinic.  A  lateral  abdominal  4-inch  incision  is  made  and  the 
ureter  is  at  once  located  in  the  pelvis  behind  the  peritoneum. 
Further  exposure  is  obtained  by  incising  the  peritoneum  midway  in 
the  pelvis,  over  the  ureter,  and  freeing  2  inches  of  the  ureter. 
At  a  point  about  i  inch  from  the  bladder  wall  the  ureter  is 
divided  between  forceps,  its  lower  end  is  ligated,  and  the  peritoneum 
is  closed  by  a  running  suture  to  the  point  at  which  the  proximal  end 
emerges.^ 

The  anastomosis  on  the  right  side  is  made  as  low  as  is  convenient. 
At  a  point  opposite  the  isolated  ureter  an  incision  i}i  inches  is  made 
through  the  outer  coats  of  the  bowel  in  the  line  of  its  longitudinal 
muscle  (Fig.  2).  The  incision  is  carried  to  the  mucous  membrane 
but  not  through  it;  a  slight  lateral  separation  is  made  of  the  tis- 
sues each  side  of  the  incision,  and  at  its  lower  end  a  puncture 
large  enough  to  insert  the  ureter  is  made  through  the  mucosa. 
The  lower  end  of  the  ureter  is  split  a  quarter  of  an  inch.  A 
curved  needle  drawing  No.  o  catgut  is  then  passed  through  and 

'  Judd  has  modified  the  operative  incision  by  making  the  lateral  abdominal  incision 
extend  to  the  peritoneum,  exp>osing  and  dividing  the  ureter  extraperitoneally,  opening 
the  peritoneum  at  the  point  of  its  ureteral  attachment,  drawing  out  a  fold  of  sigmoid, 
making  the  anastomosis  of  the  ureter  to  it  outside  the  peritoneum,  and  then  replacing 
the  bowel  within  the  peritoneum  over  the  incision  to  which  it  is  sutured. 


U"e*etera,L     operti^rtds 


W^j_ 


\ 


r 


""-Vcxrfi.n.cx 


Fig.  I.  Condition  of  Exstrophy  in  the  Female. 


EXSTROPHY  OF  THE  BLADDER 


1 103 


tied  to  the  tip  of  the  ureter;  the  short  end  of  the  thread  is  cut 
away.  The  curved  needle  is  passed  through  the  opening  into  the 

intestine  to  emerge  a  half  inch 
below  the  opening  through  the 
bowel  (see  Fig.  3).  Drawing  the 
thread  draws  the  ureteral  end 
within  the  intestine,  and  in  order 
to  tie  and  fix  the  ureter  in  f>osition, 
the  needle  is  passed  through 
a  fold  of  intestine  at  the 
point  of  emergence.  Inter- 
rupted sutures  approximate 
the  divided  peritoneum  and 
muscle  of  the  intestine  over  the 
ureter,  and  every  other  suture 
catches  a  bit  of  the  outer  wall  of 
the  ureter  securely  to  fix  its  posi- 
tion (Fig.  4).  At  the  upper  angle  of 
the  incision  an  adjacent  fat  tag  is 
caught  by  the  catgut  to  relieve  ure- 
teral pressure.  A  continuous  row  of 
sutures  makes  additional  protec- 
tion over  the  line  of  the  interrupted 
sutures;  they  extend  over  the 
suture  which  fixes  the  end  of  the 
ureter  within  the  bowel  (Fig.  5). 
Two  or  three  additional  interrupted 
sutures  adjust  the  bowel  to  the  pa- 
rietal peritoneum  in  such  a  manner 
as  to  avoid  kinking  of  the  ureter 
and  to  prevent  any  traction  on 
it.  This  method  incorp>orates  the 
ureter  into  the  wall  of  the  bowel  so  that  the  ureter,  before 
entering  the  bowel  lumen,  is  covered  internally  for  a  distance 
of  iX  inches  by  the  intestinal  mucous  membrane  only,  and  any 
internal  pressure  closes  the  ureter;  the  duct  entrance,  similar 
to  all  duct  entrances  throughout  the  body,  will  close  by  pressure 
against  ascending  gases  and  liquids,  but  it  does  not  prevent  the 


Fig.  2.  a.   Incision    in   End  of  Ureter 

6.  Incision  Made  in  Longitudinal  Band 

of  Sigmoia. 


1 104  EXSTROPHY  OF  THE  BLADDER 

normal  intermittent  emptying  of  the  ureter  by  peristalsis.  The 
right  side  should  be  operated  on  first,  as  otherwise  the  bowel  may 
be  so  shortened  by  a  primary  left  operation  as  to  make  the  right 
one  difFicuIt  of  accomphshment.  Because  of  the  fact  that  for  several 
days  after  the  first  ureter  is  transplanted  mild  uremic  symptoms 
develop  from  absorption  by  the  bowel  of  the  urine,  which  may  be 
compared  to  the  Murphy  drip,  it  is  best  to  wait  for  from  ten  to 
fourteen  days  before  the  second  operation  is  done.  Usually  within 
from  two  to  four  days  the  urine  is  passing  freely  into  the  rectum. 
Separating  the  ureter  for  the  distance  necessary  in  order  to  make  the 
anastomosis  does  not  endanger  its  vitaHty,  if  it  is  left  free  from 
tension,  as  was  shown  by  Margarucci,  Monari,  and  Krynski. 

We  agree  with  Oppel  that  some  degree  of  pyelitis  occurs  in  most 
patients  operated  on;  we  beheve,  also,  that  the  ultimate  danger  is 
increased  by  a  partial  obstruction  of  the  ureter  other  than  that 
afforded  by  pressure-control  in  the  bowel  wall.  It  is  best  to  keep  a 
perforated  rubber  tube  in  the  rectum  to  deliver  the  urine;  this  is 
more  important  after  the  second  operation.  The  third  stage  of  the 
operation  represents  the  enucleation  of  the  bladder  and  the  removal 
of  the  short  ends  of  the  ureters  attached  to  it. 

The  most  favorable  age  for  the  operation  of  exstrophy  of  the 
bladder  is  from  four  to  ten  years;  it  is  seldom  performed  after  thirty 
years.  Occasionally  young  persons  have  greatly  dilated  ureters;  after 
the  age  of  thirty,  dilated  ureters  are  more  common,  and  if  double, 
the  operation  is  inadvisable.  We  have  operated  on  children  two 
years  of  age,  but  we  do  not  recommend  it  until  they  are  old  enough  to 
attend  to  their  own  clothing  in  order  to  avoid  constant  soiling. 
Within  a  few  weeks  after  operation  children  can  retain  the  urine 
perfectly  for  from  two  to  four  hours,  while  adults  frequently  do  so 
for  from  four  to  eight  hours. 

In  our  series  of  52  patients,  6  were  operated  on  by  the  plastic 
method;  i  died  six  months  later  (traumatic  exstrophy  at  childbirth); 
3  patients  were  operated  on  by  the  Maydl-Moynihan  method,  2  of 
whom  died  of  uremia.  Twenty-six  were  operated  on  by  the  trans- 
plantation method,  22  successfully;  2  of  these  patients  had  but  one 
kidney  each.  Four  died  shortly  after  operation.  Seventeen  of  the 
52  patients  were  not  operated  on  at  the  time  of  their  examination; 
some  of  them  were  too  young  and  are  to  be  operated  on  later; 


UreteraL 
satare 


Fig.  3. 


Mucous  Membrane  Exposed  and  Opening  Maob 
IN  Mucosa  to  Receive  Ureter. 


'?'Sli^f*'^^\?C 


Sep-fcLC  an.oh.or- 


1st.  VOVJ 


w 


Fig.  4.  Closure  of  Peritoneum  and 
Muscle  over  Ureter,  Fixing  Ureter  by 
Every  Other  Suture. 


■■TJ^S^ 


FLrsi 

J 

H 

ro-ur 

1 1  ■ 

^' 

1 

n--/' 

Fig.  5.  Entire  Area  Buried  beneath 
Continuous,  Serous.  Approximating  Su- 
tures. 


EXSTROPHY  OF  THE  BLADDER  1105 

others  with  diseased  or  dilated  ureters  were  advised  aga"nst  the 
operation. 

BIBLIOGRAPHY 

1.  Albarran,  J.,  quoted  by  Zesas. 

2.  Baird,  J.  S.,  Scott,  R.  L.,  and  Sp)encer,  R.  D.,  "Studies  on  the  Trans- 

plantation of  the  Ureters  into  the  Intestines,"  Surg.,  Gynec.  €f 
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3.  Beck,   C,    "A   New   Method   of  Operation   for   Exstrophy   of  the 

Bladder,"  N.  York  M.  J.,  1900,  LXXII,  311-312. 

4.  Bereznjagowski,  quoted  by  Oppel. 

5.  Berg,  J.,    "Om   behandling  af  ectopia  vesicae,"    Hygiea,  1892,  LIV, 

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6.  Bergenhem,    B.,     "Ectopia    vesicae;     Epispadias;    lithiasis    renalis; 

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of  the  Bladder  in  the  Female,"  Lancet,  1899,  I,  161-162. 

15.  Coffey,  R.  C,  "Physiologic  Implantation  of  the  Severed  Ureter  or 

Common  Bile-Duct  into  the  Intestine,"  J.  Am.  M.  Ass.,  191 1,  LVI, 
397-403. 


iio6  EXSTROPHY  OF  THE  BLADDER 

i6.  Connell,  F.  G.,  "Exstrophy  of  the  Bladder,"  J.  Am.  M.  Ass.^  1901, 
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toires,"  Bull,  et  mem.  Soc.  de  cbir.,  1912,  XXXVIII,  2-24. 

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the  Urinary  Bladder,"  Surg.,  Gynec.  &  Obst.,  1908,  VII,  695-700. 

19.  Drucbert,  J.,  "Les  resultats  eloignes  de  I'operation  de  Maydl  dans 

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20.  Duncan,  A.,  "An  Attempt  towards  a  Systematic  Account  of  the 

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21.  Edmunds,  W.,  and  Ballance,  C.  A.,  "Diverting  the  Ureters  and  Re- 

moving the  Bladder,"  St.  Thomas's  Hosp.  Rep.,  1886,  XVI, 
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EXSTROPHY  OF  THE  BLADDER  1107 

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42.  Lower,  W.  E.,  "Malformations  and  Diverticulum  of  the  Bladder," 

Cabot,  H.,  ed.  Mod.  Urol.,  Philadelphia,  Lea  &  Febiger,  191 8,  II, 
32-65. 

43.  Makkas,  M.,  "Zur  Behandlung  der  Blasenektopie.  Umwandlung  des 

ausgeschalteten  Coecum  zur  Blase  und  der  Apjjendix  zur  Urethra," 
Centralbl.  J.  Cbir.,  1910,  XXXVII,  1073-1076. 

44.  Malone,  B.,  "A  Discussion  of  the  Different  Methods  of  Exclusion  in 

the  Treatment  of  Exstrophy  of  the  Bladder,  with  Case  Report," 
Tr.  Soutb.  Surg.  Ass.,  19 16,  XXIX,  240-246. 

45.  Margarucci,  O.,  "Ricerche  sulla  circolazione  propria  dell*  uretere," 

Policlin.,  1893-94,  I,  321-324;  also  Atti.  d.  XI  Cong.  med.  internaz., 
1894,  Roma,  1895,  IV,  563-5. 

46.  Martin,  F.  H.,  "Implantation  of  Ureters  in  Rectum,  "J.  Am.  M.  Ass., 

1899,  XXXII,  159-161. 

47.  Maydl,  K.,  "Ueber  die  Radikaltherapie  der  Ectopia  vesica  urinariae," 

Wien.  med.  Wcbnscbr.,  1894,  XLIV,  11 13;  1169;  1256;  1293;  "Neue 
Beobachten  von  Ureteren-implantation  in  die  Flexura  romana  bei 
Ectopia  vesica,"  1896,  XLVI,  1241;  1333;  1374* 

48.  Mayo,  C.  H.,  "Exstrophy  of  the  Bladder  and   its  Treatment,"  J. 

Am.  M.  Ass.,  1917,  LXIX,  2079-2081. 

49.  Mirotworzefl",  S.  R.,  quoted  by  Opf>eI. 


iio8  EXSTROPHY  OF  THE  BLADDER 

50.  Monari,  U.,  "Ueber  Ureter- Anastomosen ;  experimentelle  Untersuch- 

ungen,"  Beitr.  z.   klin.   Cbir.,    1895-96,  XV,  720-734,  quoted  by 
Connell. 

51.  Moorhead,  J.  J.  and  E.  L.,  "Exstrophy  of  the  Bladder,"  J.  Am.  M. 

Ass.,  1916,  LXVI,  409-411. 

52.  Moynihan,  B.  G.  A.,  "Extroversion  of  the  Bladder.  Relief  by  Trans- 

plantation of  the  Bladder  into  the  Rectum,"  Ann.  Surg.,   1906, 
XLIII,  237-240. 

53.  N^Iaton,  Gaz.  bebd.  de  med.,  1854,  I,  quoted  by  Connell. 

54.  Neudorfer,  J.,  "Die  Operation  der  Ectopie  der  Blase,"  Fortscbr.  d. 

Med.,  1886,  IV,  255-258;  quoted  by  Boogher,  L.,  "Exstrophy  of 
the  Bladder,"  Urol.  &•  Cutan.  Rev.,  1916,  XX,  376-377. 

55.  Oppel,  W.  A.,  "Exclusion  of  the  Bladder,  Urol.  &"  Cutan.  Rev.,  Tech. 

Suppl.,  1913,  I,  1-22. 

56.  Orlow,  L.,  "Traitement  operatoire  de  I'exstrophie  de  la  vessie;  trans- 

plantation des  uret^res  par  le  procede  de  Maydl,"  Rev.  de  gynec. 
et  de  cbir.  abd.,  1903,  VII,  795-852. 

57.  Passavant,   G.,   "Die  Blasen-Harnrohrennaht   mit  Vereinigung  der 

Schambeinspalte    bei    angeborener    Blasenspalte  und    Epispadie," 
Arcb.  J.  klin.  Cbir.,  1887,  XXXIV,  463-500;  1890,  XL,  1-61. 

58.  Pawlick,  "Ueber  Blasenexstirpation,"   Wien.  med.  Wcbnscbr.,  1891, 

XLI,  1814-1816. 

59.  Peters,   G.   A.,    "Transplantation   of  Ureters   into   Rectum    by  an 

Extraperitoneal  Method  for  Exstrophy  of  Bladder,"  Brit.  M.  J., 
1901,  I,  1538-1542. 

60.  Peterson,  R.,  "Anastomosis  of  the  Ureters  with  the  Intestine,"  J. 

Am.  M.  Ass.,  1 90 1,  XXXVI,  569-573. 

61.  Petit,  Trait,  des  mal.  cbir.,  1790,  III,  4,  quoted  by  Connell. 

62.  Roux,  J.,  "Exstrophie  de  la  vessie;  autoplastic;  insucc^s;  etablisse- 

ment  definitif  d'un  canalcutane  propre  h  maintenir  en  place  un  re- 
servoir en  caoutchouc  vulcanise,"  Union  med.,  1853,  VII,  449-453. 

63.  Rovsing,   T,    "Totalexstirpation   der   Harnblase   mit  doppelseitiger 

lumbaler   Ureterostomie,"   Arcb.  J.   klin.    Cbir.,    1907,    LXXXII, 
I 047- I 054. 

64.  Rutkowski,  M,,  "Zur  Methode  der  Harnblasenplastik,"  Centralbl.  J. 

Cbir.,  1899,  No.  16;  Editorial  in  Ann.  Surg.,  1899,  XXX,  238-243. 
6^.  Sherman,  H.  M.,  "Exstrophy  of  the  Bladder  Successfully  Treated 

by  Peters'  Method.  J.  Am.  M.  Ass.,  1905,  XLV,  890-891. 
66.  Simon,  J.,  "Ectropia  vesicae;  Operation  for  Directing  the  Orifices  of 

the  Ureters  into  the  Rectum;  Temporary  Success;  subsequent  death; 

Autopsy,"  Lancet,  1852,  11,568-570;  "Congenital  Imperfection  of 


EXSTROPHY  OF  THE  BLADDER  1109 

the  Urinary  Organs  Treated  by  Operation,"  Tr.  Path.  Soc.  Lond., 
1855,  VI,  256-258. 

67.  Smith,  T,   "An  Unsuccessful  Attempt  to  Treat  Extroversion  of  the 

Bladder  by  a  New  Operation,"  St.  Bartb.  Hosp.  Rep.,  1879,  XV, 
^9-35- 

68.  Sonnenberg,   "Die   Endresultate  operativer  Verfahren  bei   Ektopia 

vesicae,"  Deutscb.  med.  Wcbnscbr.,  1899,  XXV,  219-220. 

69.  Spooner,  H.  G.,  Report  of  a  Case  of  Exstrophy  of  the  Bladder,  with  a 

Consideration  of  Operative  Treatment,"  Boston  M.  &  S.  J.  1905, 
CLII,  546-548. 

70.  Stiles,  H.  J.,  "A  Boy  with  Extroversion  of  the  Bladder,  in  whom  the 

Ureters  had  been  Transplanted  into  the  Rectum  after  the  Method 
of  Peters,  of  Toronto,"  Tr.  Med.-Cbir.  Soc.  Edinb.,  1902-03,  n.s., 
XXII,  133-135;  "Epispadias  in  the  Female  and  its  Surgical  Treat- 
ment," Surg.,  Gynec.  €f  Obst.,  191 1,  XIII,  127-140. 

71.  Subbotin,   M.,   "Neues  Verfahren  zur  Bildung  der  Harnblase  und 

HarnrShre  mit  einem  Sphinkter  aus  dem  Mastdarm  bei  Exstrophia 
Vesicae,  Epispadie  hohen  Grades  und  Urininkontinenz,"  Centralbl. 
J.  Cbir.,  1 90 1,  XXVIII,  1 257-1 260. 

72.  Summers,  quoted  by  Bottomley. 

73.  Sweet,  J.  E.,  and  Stewart,  L.  F.,  "The  Ascending  Infection  of  the  Kid- 

neys," Surg.,  Gynec.  €f  Obst.,  1914,  XVIII,  460-469. 

74.  Thiersch,  C,  Verbandl.  d.  deutscb.  Gesellscb.  J.  Cbir.,  1882,  XI,  89; 

also  Centralbl.  f.  Cbir.,  1876,  504,  quoted  by  Connell;  "Zwei  Ffille 
von  operativ  geheilter  Inversio  vesicae,"  Berl.  klin.  Wcbnscbr.,  1892, 
XIX,  471. 

75.  Tichow,  quoted  by  Oppel. 

76.  Trendelenburg,  F.,  "Zur  Operation  der  Ectopia  vesicae,"  Centralbl.  f. 

Cbir.,  1885,  XII,  857-860;  "Ueber  Operationen  zur  Heilung  der 
angeborenen  Harnblasen-  und  HarnrShrenspalte,"  Arcb.J.  klin.Cbir., 
1892,  XLIII,  Festschr.,  394-438. 

77.  Verhoogen,  J.,  "Neostomie  uretero-caecale;  formation  d'une  nouvelle 

poche  v6sicale  et  d'un  nouvel  ur^tre."  Ass.  Jrang.  d^urol.  Proc.' 
verb.,  1908,  Paris,  1909,  XII,  362-365. 

78.  Watson,  F.  S.,  "The  Operative  Treatment  of  Tumors  of  the  Bladder," 

Ann.  Surg.,  1905,  XLII,  805-830. 

79.  Werelius,  A.,  "Operative  Method  for  Exstrophy  of  Bladder;  with 

Report  of  a  Case,"  Surg.,  Gynec.  &•  Obst.,  191 1,  XII,  158-159. 

80.  Winslow,  R.,  "Report  of  a  Case  of  Exstrophy  of  the  Bladder  Operated 

on  Nearly  Thirty  Years  Ago,  with  Subsequent  History,"  Surg., 
Gynec.  if  Obst.,  1916,  XXII,  350-352. 


mo  EXSTROPHY  OF  THE  BLADDER 

8i.  Witzel,  C,  "Zur  Technik  der  Magenfistelanlegung,"  Centralbl.  J. 
Cbir.f  1891,  XVIII,  601-604;  "Die  Sicherung  der  Gastroenteros- 
tomose  durch  Hinzufiigung  einer  Gastrostomose  (Gastroenteros- 
tomosis   externa),"   Centralbl.  f.    Cbir.,    1899,   XXVI,    1193. 

82  Witzel,  0.,  and  Hoffman,  C,  "Die  Gastroenterostomosis,  Gastrosto- 
mosis  und  ihre  Verbindung  zur  Gastroenterostomosis  externa," 
Deutscb.  med.  Wcbnscbr.,  1900,  XXVI,  301-303;  325-327;  342-346. 

83.  Wood,  J.,  "Exstrophy  of  the  Bladder,"  Brit.  M.  J.,  1880,  I,  278. 

84,  Zesas,  D.  G.,  "Die  Implantation  der  Ureteren  in  den  Darm,"  Deutscb. 

Ztscbr.  j.  Cbir.y  1909,  CI,  233-266. 


SOME  NOTES  ON  ACHYLIA  GASTRICA 
By  Thomas  R.  Brown,  M.D.,  Baltimore,  Md. 

IN  discussing  achylia  gastrica,  or,  to  be  more  exact,  achlorhydria 
met  with  in  other  conditions  than  pernicious  anemia,  it  is  well 
to  note  at  first  the  steady  increase  in  the  number  of  conditions, 
functional  as  well  as  organic,  in  which  absence  of  free  hydrochloric 
acid  is  met  with  in  a  greater  or  less  proportion  of  cases. 

Let  us  simply  enumerate  some  of  these;  some  obviously  to  be 
regarded  as  of  primary  or  essential,  others  of  definitely  secondary 
type,  and  in  these  various  pathological  entities  we  find  representa- 
tives of  all  the  theoretically  possible  causes  from  the  pathological- 
physiological  standpoint;  psychogenic,  neurogenic,  reflex,  toxic, 
inflammatory,  infectious,  due  to  disturbance  in  blood  supply,  to 
errors  of  metabolism,  to  disturbance  of  the  normal  secretory  stim- 
uli of  nervous,  or  of  hormonic  origin.  In  the  p>ost-mortem  study 
of  these  cases  we  therefore  find,  as  we  would  expect,  very  marked, 
or  very  slight,  or  no  pathological  changes  in  the  glands  devoted  to 
secretion  of  acid  and  pepsin,  while  part  passu  with  this  we  find, 
clinically,  that  in  certain  cases  a  complete  return  of  normal  secre- 
tion is  possible,  in  other  cases  a  partial  return,  while  in  still  others 
the  lack  of  acid  and  pepsin  is  a  permanent  condition. 

Let  us  run  over,  seriatim,  the  most  imp)ortant  pathological 
conditions  in  which  complete  absence  of  free  and  combined  hydro- 
chloric acid,  and,  according  to  our  exf>eriments,  as  a  rule,  marked 
diminution  or  absence  of  pepsin  is  met  with. 

1 .  The  last  stages  of  chronic  gastritis — alcoholic,  due  to  dietetic 
errors,  or  due  to  teeth,  tonsillar,  nasal,  pharyngeal  infections,  etc. 

2.  Gout  and  arthritis  deformans,  or,  p)erhaps,  better  called 
chronic  infectious  arthritis,  leading  in  the  first  case  to  the  substitu- 
tion of  an  acid  for  an  alkaline  therapy,  and  in  the  latter  to  the  belief 
held  by  many  in  the  intestinal  origin  of  the  disease. 

3.  Various  infectious  diseases — tuberculosis,  where  it  is  often 
found,  and  typhoid  fever,  in  the  latter  of  which  in  a  number  of  cases 


1 1 12        SOME   NOTES   ON   ACHYLIA   GASTRICA 

we  have  found  a  complete  achylia  following  the  disease,  which  may 
be  one  of  the  causes  of  the  gastrointestinal  symptoms  often  met 
with,  which  is  probably  toxic  in  origin  and  not  due  to  destructive 
changes  in  the  glands,  as  in  many  cases,  after  a  considerable  period 
of  time — in  several  of  our  cases  more  than  a  year — there  was  a 
gradual  return  to  normal  gastric  juice,  and  in  all  these  cases  the  use 
of  hydrochloric  acid  therapy  should  be  advised;  syphilis,  sinusitis, 
pyorrhea  alveolaris — a  very  frequent  cause,  probably  leading  to  a 
true  infectious  gastritis,  and  being  the  most  potent  factor  in  the 
gastric  dyspepsia  and  diarrhea  in  older  people — and  tonsillitis. 

4.  Various  intestinal  parasitic  diseases,  especially  infection  with 
the  uncinaria — hookworm  disease,  though  frequently  found  in  in- 
fections with  tapeworm,  round  worm,  and  entamoeba,  peculiarly 
interesting  as  an  expression  of  a  toxic  achylia  of  intestinal  origin, 
and  thus  of  especial  interest  in  connection  with  pernicious  anemia. 
Incidentally,  a  blood  picture  very  similar  to  that  of  pernicious 
anemia  may  be  produced  by  repeated  injections  of  the  juice  ex- 
pressed from  certain  of  these  parasites. 

5.  Conditions  associated  with  chronic  passive  congestion,  notably 
chronic  nephritis  and  myocardial  disease. 

6.  Pellagra  and  sprue — in  the  latter  associated  frequently  with 
a  concomitant  absence  of  pancreatic  secretion,  and  in  each  disease 
a  marked  improvement  of  the  digestive  symptoms  often  following 
the  administration  of  hydrochloric  acid,  in  association  with  pan- 
creatic ferment  in  the  case  of  sprue,  with,  in  the  latter,  a  return  to 
normal  gastric  contents  and  the  marked  improvement  of  general 
symptoms  met  with  in  quite  a  number  of  these  cases. 

7.  Cancer,  not  only  of  the  stomach,  but  often  of  other  organs, 
even  outside  the  abdominal  cavity,  especially  in  the  late  stages  of 
the  disease. 

8.  Diseases  of  the  thyroid;  and  here,  both  in  Graves's  disease,  or 
hyperthyreosis,  and  myxedema,  or  hypothyreosis,  it  is  often  found, 
and  is  probably  the  cause  of  the  marked  diarrhea  which  may  be  the 
only  symptom  of  the  former  disease. 

9.  Linitis  plastica,  or  cirrhosis  of  the  stomach,  probably  repre- 
senting, in  most  cases,  the  conversion  of  an  old  ulcer  into  a  malig- 
nant condition,  with  marked  hyperplasia  of  the  fibrous  tissue  and 
very  little  cellular  participation. 


SOME   NOTES   ON   ACHYLIA   GASTRICA        1113 

10.  High  grades  of  ptosis  and  atony  of  the  stomach,  although 
here  hyperacidity  or  normal  acidity  may  also  be  found. 

11.  Chronic  gall-bladder  disease  with  and  without  jaundice, 
where  we  have  found  it  in  a  very  considerable  proportion  of  cases, 
and  where  it  may  prove  of  real  aid  in  diagnosis. 

12.  After  sudden  shock,  violent  emotions,  worry,  and  overwork, 
also  frequently  during  the  menstrual  period. 

Truly  a  large  group  of  cases,  and  very  interesting,  as  it  makes 
one  realize  under  what  various  stimuli — infectious,  toxic,  nervous, 
etc. — the  condition  may  develop,  and  how  difficult  it  may  be  to 
differentiate  the  true  underlying  condition.  Unlike  many  others, 
we  have  not  found  the  presence  of  pepsin  in  large  amount  of  much 
value  in  differentiating  the  purely  functional  from  the  organic 
achlorhydrias,  for  in  a  large  series  in  which  the  pepsin  was  estimated 
quantitatively  by  the  edestin  method  we  found  in  the  great  ma- 
jority of  cases,  both  functional  and  organic,  the  practical  disap- 
pearance of  pepsin  pari  passu  with  that  of  the  hydrochloric  acid. 
The  eflFect  of  the  absence  of  hydrochloric  acid  is  very  varied,  and  in 
many  cases  difficult  to  explain,  as,  for  example,  the  fact  that  in 
certain  cases  it  is  associated  with  a  diarrhea,  in  others  with  consti- 
pation, and  in  still  others  with  a  normal  bowel  habit.  After  all, 
to  appreciate  what  the  absence  of  hydrochloric  acid  may  bring  about 
we  must  always  keep  in  mind  its  multiplex  functions — its  action 
upon  the  pyloric  sphincter;  its  role  in  converting  the  inactive  pro- 
secretin into  the  active  hormone  of  the  pancreas,  secretin;  its  disin- 
fecting properties;  its  role  in  the  digestion  of  the  proteins;  the 
essential  part  it  plays  with  pepsin  in  the  digestion  of  connective 
tissue,  and  its  activating  p>ower  upon  the  zymogens  of  pepsin  and 
rennin. 

There  are  certain  peculiarly  interesting  problems  which  arise 
in  connection  with  the  study  of  this  subject,  as,  for  example,  the 
rather  striking  increase  in  the  soluble  proteid  contents  of  the  gastric 
contents  in  the  achylia  met  with  in  carcinoma,  of  real  value  in  differ- 
ential diagnosis;  our  demonstration  by  stool  studies  that  in  prac- 
tically all  the  achylias  except  those  met  with  in  sprue,  the  pancreatic 
ferments  are  practically  normal  in  quality.  This  is  interesting,  in 
the  first  place,  in  calling  attention  to  the  fact  that  we  must  assume 
a  nervous,  as  well  as  a  hormonic  mechanism  in  the  elaboration 


1 1 14        SOME   NOTES   ON   ACHYLIA   GASTRICA 

of  the  pancreatic  secretions — at  least,  in  pathological  conditions — 
thus  supporting  Pawlow's  views  (and  opposing  those  of  Starling), 
that  hormonic  stimulation  cannot  explain  the  whole  phenomenon  of 
secretion  in  the  gastrointestinal  tract  below  the  gastric  level,  and, 
in  the  second  place,  definitely  opposing  Gross's  view  that  in  gastro- 
genous  diarrheas  met  with  in  achylia  there  is  a  concomitant  diminu- 
tion of  pancreatic  ferments. 

Another  point  of  great  interest,  and  one  which  has  not  yet  been 
satisfactorily  explained,  is  why  certain  achylias  are  associated  with 
diarrhea,  others  with  normal  motor  function  of  the  bowels,  others 
with  hypomotility;  certainly  not  to  be  explained  in  our  experience 
on  the  theory  that  in  the  herbivor  type  the  achylias  are  likely  to  be 
associated  with  diarrhea,  in  the  carnivor  type  with  constipation; 
and  in  the  second  place,  the  minimum  amount  of  hydrochloric 
acid  which  is  necessary — not  more  than  a  few  per  cent  of  the  normal 
amount  secreted  with  an  ordinary  meal,  which  can  absolutely  con- 
trol the  diarrhea  in  the  majority  of  these  cases.  Another  point  of 
peculiar  interest  is  the  extreme  hypersensitiveness  to  acid  medication 
met  with  in  certain  of  these  cases  of  achylia  gastrica — a  few  drops 
of  any  acid,  even  lactic  or  citric  acid,  producing  marked  discomfort, 
even  great  pain;  and  in  the  last  place  the  frequency  with  which,  if 
gastric  symptoms  are  present,  they  simulate  symptoms  of  hyper- 
chlorhydria,  which  is  probably  best  explained  by  the  associated 
vagal  hyperesthesia  met  with  in  both  cases;  and  last  of  all,  in  the 
great  majority  of  these  cases  of  achylia  the  gastric  symptoms  are 
very  slight  or  nil,  the  symptoms  dominating  the  picture  being 
ahnost  entirely  intestinal. 


EPIDEMIC  PNEUMONIA 
By  W.  G.  Mac0.llum,  M.D., 

The  Johns  Hopkins  University,  Baltimore 

THE  history  of  medicine  records  many  epidemics  of  pneumonia, 
sometimes  in  association  with  other  diseases,  sometimes 
spreading  independently.  No  very  precise  idea  of  the  nature 
of  these  epidemics  or  of  the  reasons  for  their  epidemic  character  can 
be  derived  from  these  records,  because  nearly  all  occurred  before 
the  era  of  bacteriological  studies,  but  the  epidemics  of  the  year 
19 1 8  should  furnish  much  material  for  the  solution  of  these  problems, 
since  they  have  been  very  diligently  studied. 

It  appears  that  there  were  in  the  United  States  two  great  epidemic 
outbreaks  of  pneumonia,  the  first  closely  associated  with  measles, 
lasting  through  the  winter  and  spring,  the  second  immediately 
following  the  sudden  sweep  of  influenza  across  the  continent  in  the 
late  summer  and  autumn.  In  the  interval  there  were  small  epidemics 
here  and  there,  but  nothing  that  attracted  general  attention.  It  is 
true  that  during  the  season  in  which  lobar  pneumonia  ordinarily 
occurs  there  were  scattered  cases  of  this  disease  in  about  the  usual 
proportion. 

The  First  Epidemic.  In  the  winter  and  spring  measles  was 
extremely  prevalent  among  the  men  of  the  drafted  troops  who  came 
from  remote  rural  districts.  It  had  the  ordinary  characters,  but 
cultures  and  smears  showed  that  many  of  these  men  harbored  in 
their  throats  a  hemolytic  streptococcus.  This  readily  spread  in 
crowded  wards  to  the  throats  of  others.  It  was  thought  and  after- 
ward proven  that  if  the  clean  measles  patients  could  be  kept  sep- 
arate from  those  with  infected  throats  most  of  the  pneumonia  might 
be  avoided. 

The  deaths  in  this  pneumonia  followed  a  brief  but  severe  illness, 
the  outstanding  features  of  which  were  extreme  inspiratory  dyspnea 
with  a  livid  cyanosis,  and  in  most  cases  the  signs  of  extensive 
pleural  eff"usion.   There   was   usually   a  definite   leucocytosis.   At 

1115 


iii6  EPIDEMIC  PNEUMONIA 

autopsy  the  lungs  presented  a  great  variety  of  conditions,  but  the 
study  of  a  long  series  of  cases  appears  to  permit  one  to  consider  these 
under  two  main  headings,  although  combinations  of  these  must  be 
recognized.  In  each  of  these  groups  several  stages  are  distinguishable, 
and  the  presence  of  an  abundant  pleural  effusion  may  introduce 
modifications  of  another  kind.  It  seems  permissible  to  anticipate 
what  must  be  written  of  the  details  of  these  conditions  and  to 
present  the  view  that  in  the  first  of  these  groups  we  have  the  effect 
of  bacteria  invading  the  tissues  of  a  resistant  host,  while  in  the 
second  the  host  displays  very  shght  resistance.  The  frequent  com- 
bination of  the  lesions  characteristic  of  these  groups  would  suggest 
that  the  lowering  of  resistance  may  be  due  to  the  production  of  an 
allergic  or  hypersensitive  state. 

In  practically  all  of  these  cases  a  hemolytic  streptococcus  was 
the  predominant  organism,  and  this  was  distributed  in  such  relation 
to  the  lesions  that  there  could  be  no  doubt  of  its  significance  as  the 
essential  cause  of  the  pneumonia.  In  some  cases  the  influenza 
bacillus  of  Pfeiffer  was  also  present,  and  in  two  or  three  it  was  the 
predominant  organism  in  the  lung,  so  that  those  rather  pecuhar 
cases  were  regarded  as  illustrating  the  lesions  produced  by  that 
bacillus.  The  pneumococcus  was  present  in  some  cases  in  areas  of 
typical  lobar  pneumonia,  while  the  rest  of  the  lung  was  occupied  by 
characteristic  streptococcal  pneumonia. 

Interstitial  Broncho-pneumonia.  This  name  has  been  given  to  the 
combination  of  bronchitis  and  nodular  consohdation  produced  by 
the  streptococcus  in  the  lungs  of  a  resistant  person.  It  is  primarily 
a  purulent  bronchitis  with  a  zone  of  hemorrhage  about  each  bron- 
chiole, and  intense  infiltration  of  the  bronchial  wall  with  leucocytes 
and  mononuclear  cells.  The  streptococci  remain  almost  entirely 
restricted  to  the  purulent  exudate  in  the  bronchi,  and  although  they 
are  found  in  numbers  in  the  lymphatics  of  the  lung,  through  which 
they  extend  to  infect  the  pleura,  they  are  not  found  in  the  alveolar 
exudate. 

In  the  more  advanced  stages  the  bronchi  are  still  found  to 
contain  a  purulent  exudate,  but  their  walls  are  enormously  thickened 
by  the  great  vascularization,  new  formation  of  granulation  tissue, 
and  especially  by  an  extraordinary  accumulation  of  mononuclear 
wandering  cells  in  the  interstices  of  the  tissue.  The  epithelium  is 


EPIDEMIC  PNEUMONIA  1117 

merged  into  a  necrotic  false  membrane  or  has  disappeared.  Strep- 
tococci lie  in  great  numbers  along  the  lining  surface  of  the  bronchiole. 
The  neighboring  alveoli  are  filled  with  dense  plugs  of  fibrin  together 
with  desquamated  epithelial  cells,  lymphoid  cells,  and  red  corpuscles. 
The  alveolar  walls  are  greatly  thickened  by  an  infiltration  of  the 
same  mononuclear  cells  and  by  new  formation  of  connective  tissue. 
This  fades  away  in  alveoli  more  distant  from  the  bronchiole,  but 
reappears  to  some  extent  in  the  neighborhood  of  the  interlobular 
septa.  The  alveolar  exudate  also  changes  in  character  as  one  passes 
away  from  the  bronchi  and  the  dense  plugs  of  fibrin,  which  are  often 
partly  replaced  by  vascular  connective  tissue,  disappear,  and  give 
place  to  blood  and  finally  to  a  viscid  fluid. 

The  interlobular  septa  are  greatly  thickened  by  edema,  infil- 
tration with  mononuclear  wandering  cells,  and  the  new  formation  of 
connective  tissue,  and  are  rendered  especially  conspicuous  by  the 
great  distention  of  the  accompanying  lymphatics  with  a  purulent 
clot  rich  in  bacteria.  There  can  be  no  stream  of  lymph  in  such  an 
occluded  channel,  and  the  streptococci  must  reach  the  pleura  by 
actual  growth  rather  than  by  any  passive  transportation.  The 
pleura  is  thickened  by  a  newly  formed  granulation  tissue  and  is 
covered  with  a  fibrinopurulent  exudate. 

The  gross  appearance  of  the  lung  corresponds  with  these  pro- 
gressive changes.  In  the  beginning  the  surface  is  smooth,  there  is  no 
fluid  in  the  pleural  cavity,  and  the  lung  is  distended  with  air.  On 
the  cut  surface  the  bronchi  and  bronchioles  can  be  traced  by  their 
thickened  gray  walls,  their  content  of  grayish-yellow  pus,  and  the 
halo  of  hemorrhage  which  surrounds  them.  In  later  stages  the 
pleural  cavity  contains  a  quantity  of  thin,  greenish-brown  fluid  with 
a  granular  sediment  and  shreds  of  fibrin.  The  pleural  surface  is 
covered  with  shaggy  fibrin  unevenly  distributed  and  the  pleura 
itself  is  thickened.  The  lung  is  collapsed,  partly  as  a  result  of  the 
obstruction  of  the  bronchi,  partly  from  the  pressure  of  the  pleural 
eff"usion.  Throughout  its  substance  there  can  be  felt  firm  nodules  or 
more  extensive  masses  of  consolidated  tissue.  Upon  the  cut  surface 
the  lobules  are  marked  out  very  distinctly  by  the  conspicuously 
thickened  interlobular  septa,  which  sometimes  appear  as  prominent 
white,  beaded  bands.  In  the  lobules  there  are  usually  several  firm 
nodules  clustered  about  the  terminal  branches  of  the  bronchiole, 


iii8  EPIDEMIC  PNEUMONIA 

each  showing  in  its  center  the  lumen  of  a  bronchiole  filled  with  pus. 
If  these  bronchioles  happen  to  be  cut  longitudinally,  it  is  seen  that 
their  walls  are  greatly  thickened  and  that  the  firm  nodule  forms  a 
mantle  about  them  for  a  short  distance.  This  is  surrounded  by  a 
zone  of  hemorrhage  and  edema.  In  still  older  cases  such  peribronchial 
areas  extend  so  as  to  become  confluent  and  form  quite  large  patches 
of  consolidation,  which  are  sometimes  pale  yellow  with  a  background 
of  hemorrhage.  Retrogression  may  occur  if  the  patient  survives 
longer  and  the  pleural  exudate  assumes  a  purulent  character,  and 
unless  evacuated  is  encapsulated  by  dense  adhesions. 

Lobular  Pneumonia.  The  other  type  of  pneumonia  caused  by 
invasion  of  the  hemolytic  streptococcus  in  the  lung  of  a  less  resistant 
person  presents  none  of  the  barricading  process  just  described  and 
none  of  the  restriction  of  the  growth  and  spread  of  the  streptococci. 
The  name  lobular  pneumonia  is  arbitrarily  given,  although  perhaps 
not  entirely  suitable,  to  distinguish  it  from  the  interstitial  broncho- 
pneumonia. In  these  cases,  which  run  a  rapid  course,  there  is  no 
marked  reaction  in  the  framework  of  the  lung.  The  streptococci  are 
present  in  enormous  numbers  in  the  purulent  and  hemorrhagic 
bronchial  exudate  and  in  equally  great  numbers  in  the  bloody 
purulent  exudate  in  the  alveoli  throughout  considerable  areas.  They 
grow  into  a  perfect  feltwork  of  chains,  as  though  in  the  best  possible 
culture  medium.  The  bronchial  and  alveolar  walls  are  not  infiltrated 
with  wandering  cells,  but  together  with  the  contained  exudate 
become  necrotic  throughout  large  areas. 

The  gross  appearance  of  the  lung  corresponds  precisely  with  this. 
There  is  usually  a  bloody  pleural  exudate;  the  pleural  surface  is 
hemorrhagic  and  roughened  by  fibrin.  The  partly  collapsed  lung 
contains  confluent  areas  in  which  the  consolidated  tissue  is  deep  red 
or  almost  black  as  a  result  of  the  abundant  hemorrhage,  but  there  are 
areas  of  gray  opaque  tissue  where  necrosis  is  most  advanced.  There 
are  no  nodular  consolidations  about  the  bronchi,  and  interlobular 
septa  and  bronchial  walls  are  inconspicuous,  although  the  lymphat- 
ics may  be  distended  with  purulent  and  bloody  exudate. 

It  is  by  no  means  uncommon  to  find  small  patches  of  intra-alveo- 
lar  purulent  and  hemorrhagic  exudate,  with  abundant  streptococci, 
scattered  in  the  tissue  in  cases  in  which  the  predominant  changes  are 
those  of  the  interstitial  broncho-pneumonia.  It  seems  that  this  may 


EPIDEMIC  PNEUMONIA  1119 

be  explained  as  the  result  of  hypersensitization  of  the  tissue  pro- 
duced by  the  original  resisted  infection. 

The  Second  Epidemic.  The  epidemic  disease,  influenza,  as  all 
know,  swept  with  great  rapidity  over  the  whole  country  from  east 
to  west.  Its  nature  is  still  entirely  obscure,  in  spite  of  the  diligent 
studies  made  in  every  camp  laboratory  and  hospital.  The  view  which 
at  first  seemed  most  plausible,  that  it  was  due  to  the  influenza 
bacillus  of  Pfeiff"er,  has  not  been  substantiated  by  any  proof,  al- 
though this  organism  has  been  found  in  the  throats  and  even  in  the 
lungs  in  a  great  number,  perhaps  in  the  majority  of  cases.  It  is, 
however,  known  to  be  a  common  inhabitant  of  the  throats  of  normal 
persons,  and  might  be  expected  to  occur  with  increased  prevalence 
among  people  whose  resistance  was  lowered  by  such  a  disease  as 
epidemic  influenza,  just  as  the  pneumococcus  and  other  organisms 
were  more  frequently  found  in  significant  numbers  in  these  throats. 

In  some  districts  the  influenza  bacillus  was  found  in  practically 
every  case — in  others  only  rarely.  There  has  been  much  difficulty 
with  the  cultivation  of  this  organism,  since  it  requires  special  media 
for  its  growth.  Even  the  media  which  contain  hemoglobin  are  viti- 
ated, as  Rivers  shows,  by  the  presence  of  inhibitory  substances  in 
certain  sera.  This  may  explain  the  lack  of  success  experienced  by 
some  investigators  in  its  cultivation,  but  it  scarcely  justifies  the 
more  successful  in  other  parts  of  the  country  in  their  claim  that 
influenza  bacilli  are  really  equally  prevalent  everywhere. 

The  epidemic  influenza  has  many  of  the  characters  of  an  acute 
exanthematic  disease  such  as  measles.  Bloomfield  has  observed  a 
rash  in  many  cases  and  a  characteristic  enanthem,  and  has  also  found 
that,  as  in  measles,  the  von  Pirquet  reaction  fails  during  the  height 
of  the  disease,  only  to  appear  when  the  fever  is  over.  It  is  accompa- 
nied by  a  marked  leukopenia  and  other  evidences  of  an  extreme 
lowering  of  resistance  to  bacterial  invasion. 

The  pneumonia  which  followed  the  influenza  was  extraordinarily 
fatal,  and  was  characterized  especially  by  its  rapid  course  and  by  the 
abundance  of  the  bacteria  found  in  the  exudate.  The  anatomical 
type  of  the  pneumonia  itself  was  determined  by  the  character  of 
the  invading  organism,  and  while  there  were  often  mixed  infections, 
there  was,  as  a  rule,  one  predominating  organism  which  established 
the  type.  In  our  own  experience  the  influenza  bacillus  was  by  no 


1 120  EPIDEMIC  PNEUMONIA 

means  always  present.  Cultures,  animal  inoculations,  smears,  and 
especially  accurate  staining  of  the  sections  of  the  lungs  showed 
this.  On  the  other  hand,  when  it  was  present  in  predominant  numbers 
it  produced  a  perfectly  characteristic  type  of  pneumonia.  At  Camp 
Lee  in  Virginia  and  at  the  Johns  Hopkins  Hospital  in  Baltimore  it 
was  rarely  found,  while  at  Camp  Dix  in  New  Jersey  it  was  present 
in  every  case. 

The  organisms  concerned  were  the  several  types  of  pneumococ- 
cus,  the  staphylococcus  aureus,  the  hemolytic  streptococcus,  and 
the  influenza  bacillus. 

The  pneumonia  caused  by  the  pneumococcus  was  a  confluent 
lobular  pneumonia  which  in  late  stages  assumed  the  form  of  lobar 
pneumonia.  In  the  most  acute  cases  there  was  no  pleural  exudate; 
the  pleural  surfaces  showed  blotches  of  opaque  bloody  discoloration 
like  red  paint.  There  were  indefinite  or  sharply  lobular  patches  of 
consohdation.  On  section  these  areas  were  red,  smooth,  elastic,  fairly 
firm,  and  elevated  above  the  surrounding  tissue.  They  were  extremely 
moist  and  exuded  a  viscid  bloody  fluid.  A  gelatinous  red  fluid  could 
be  seen  in  the  terminal  bronchioles  and  ductuh  alveolares — no  plugs 
of  opaque  exudate  projected  from  the  alveoli.  The  bronchi  were 
sHghtly  reddened  or  pale,  and  contained  only  a  frothy  fluid.  Later 
stages  showed  patches  in  the  center  of  such  elastic  areas,  in  which 
the  alveoli  were  filled  with  opaque  fibrinous  plugs,  and  finally  this 
appearance  spread  to  the  whole  area  and  to  adjacent  confluent  areas 
of  consolidation. 

Microscopically  the  early  stages  showed  an  extremely  fresh, 
delicate  exudate  of  fibrin  with  red  corpuscles,  leucocytes,  and  mono- 
nuclear cells  in  the  alveoli.  The  ductuli  alveolares  were  distended 
with  fluid  and  lined  with  a  rather  thick  layer  of  hyaline  material, 
which  overlay  the  epithelium  and  failed  to  give  the  reactions  for 
fibrin.  Pneumococci  were  present  in  the  exudate  in  enormous  num- 
bers. 

The  pneumonia  caused  by  the  hemolytic  streptococcus  was 
precisely  like  that  described  as  lobular  pneumonia  in  the  first  epi- 
demic, although  it  seemed  that  the  streptococci  were,  if  possible, 
more  abundant  than  before,  and  had  caused  more  widespread  necro- 
sis and  hemorrhage.  There  was  great  edema,  the  bronchi  being  filled 
with  frothy  fluid.  No  trace  of  the  interstitial  infiltration  and  indura- 


EPIDEMIC  PNEUMONIA  1121 

tion  so  commonly  seen  in  the  form  which  followed  measles  was  to  be 
observed  in  these  cases.  It  is  to  be  noted  that  recent  reports  which 
describe  pneumonia  occurring  months  after  the  epidemic  of  influenza 
had  passed  over,  state  that  the  proportion  of  cases  due  to  the  hemo- 
lytic streptococcus  is  very  greatly  increased.  It  is  suggested  that  as  a 
result  of  frequent  passage  through  human  beings  this  streptococcus 
has  acquired  a  great  virulence,  which  permits  it  to  invade  the  lungs 
of  normal  persons  without  the  assistance  of  a  predisposing  disease. 

The  pneumonia  following  infection  with  the  staphylococcus  aureus 
was  not  well  represented  in  our  series,  since  we  had  only  a  few  cases 
in  which  there  was  a  mixed  infection,  but  Dr.  Chickering,  who 
observed  many  cases,  describes  it  as  a  specific  form  in  which,  upon 
the  basis  of  a  rather  difi^use  inflammatory  process,  minute  abscesses 
ultimately  develop  throughout  the  lung.  In  these  the  organisms  are 
present  in  great  numbers. 

The  pneumonia  caused  by  the  influenza  bacillus  of  Pfeiff"er  seems 
to  have  been  common  in  the  New  England  States.  We  encountered 
a  number  of  cases  in  the  epidemic  at  Camp  Dix  in  which  the  influ- 
enza bacillus  was  the  predominant  organism  and  sometimes  present 
in  pure  culture.  In  these  there  was  a  pneumonic  lesion  entirely 
diff^erent  from  those  caused  by  the  pneumococcus  or  streptococcus. 
It  resembled,  rather,  the  interstitial  broncho-pneumonia,  and  may 
be  most  accurately  described  by  that  name.  The  bacilli  often  in 
large  numbers  were  restricted  to  the  bronchi.  None  were  found  in 
the  lymphatics,  which  were  collapsed  and  inconspicuous,  nor  were 
any  found  in  the  pleural  cavity,  since  in  most  cases  this  was 
obhterated  by  adhesions. 

The  bronchial  exudate  was  composed  of  polymorphonuclear 
leucocytes,  many  of  which  were  active  phagocytes.  The  bronchial 
walls  were  enormously  thickened,  not  only  by  infiltration  with  leu- 
cocytes and  lymphoid  and  plasma  cells,  but  also  by  an  extensive 
new  growth  of  connective  tissue  cells.  The  adjacent  alveoH  con- 
tained dense  plugs  of  fibrin  with  desquamated  epithelial  cells  and 
many  leucocytes.  There  was  no  great  admixture  of  red  blood  cor- 
puscles, but  widespread  organization  of  the  exudate  had  occurred. 
The  exudate  diff"ered  from  that  seen  in  the  streptococcal  interstitial 
broncho-pneumonia  in  the  greater  proportion  of  leucocytes  found 
there.  No  influenza  bacilli  were  found  in  this  alveolar  exudate.  The 


1 122  EPIDEMIC  PNEUMONIA 

alveolar  walls  were  greatly  thickened  by  a  process  identical  with 
that  in  the  bronchial  walls. 

The  gross  appearance  of  such  a  lung  was  entirely  different  from 
that  of  the  lung  in  which  pneumonia  was  caused  by  the  pneumococ- 
cus.  These  lungs  were  rather  pale  and  dry,  the  bronchi  filled  with 
thick,  yellow,  sticky,  purulent  exudate.  The  pleural  surface  was 
smooth  or  roughened  by  adhesions.  Most  of  the  lung  substance  was 
air-containing,  but  studded  throughout  with  firm,  shot-like  nodules 
and  some  larger  solid  masses.  Upon  incision  these  were  found  in 
relation  to  the  bronchioles  as  prominent  yellow  nodules,  the  cut 
surface  of  which  was  dense,  smooth,  and  shining,  sometimes  rather 
gray  and  translucent,  and  showing  in  the  center  the  lumen  of  a 
bronchiole  filled  with  pus.  The  larger  areas  were  obviously  due  to 
the  confluence  of  such  nodules. 

This  condition  is,  therefore,  in  every  respect  comparable  with 
the  interstitial  broncho-pneumonia  caused  by  the  streptococcus, 
although  it  seems  to  indicate  that  since  such  resistance  and  barricade 
formation  can  be  evidenced  in  a  person  recently  aff'ected  by  the 
influenza,  the  virulence  of  the  influenza  bacillus  must  be  less  than 
that  of  the  streptococcus.  It  emphasizes  this  analogy  to  find  that  in 
certain  cases  there  are,  in  addition  to  the  nodules  of  interstitial  in- 
filtration with  organized  exudate,  patches  of  alveoli  which  are  thin- 
walled,  but  filled  with  an  exudate  of  leucocytes  with  myriads  of 
influenza  bacilli.  This  is  quite  comparable  with  the  combinations 
of  interstitial  broncho-pneumonia  with  patches  of  lobular  pneu- 
monia in  the  streptococcal  infection,  in  which,  although  the  strep- 
tococci have  been  restrained  for  a  long  time,  they  finally  thrive  in 
certain  patches  of  the  newly  sensitized  tissue. 

Although  it  is  possible  to  distinguish  the  forms  of  pneumonia 
caused  by  the  invasion  of  diff^erent  bacteria  in  tissue  prepared  for 
their  reception  by  predisposing  disease,  the  nature  of  the  pre- 
disposing diseases  measles  and  influenza  remains  obscure. 


A   PSYCHO-THERAPEUTIC   CLINIC   IN   THE    JURA 

MOUNTAINS 

By  C.  F.  Martin,  M.D.,  Montreal 

IT  is  a  far  cry  from  the  mysteries  of  Osiris  and  Eleusis  to  the  more 
patent  quasi-religious  miracles  of  Notre  Dame  de  Lourdes,  and 
from  the  healing  powers  of  the  "Divine  Physician"  to  the  days 
of  modern  occultism.  Each  era  throughout  the  centuries  has  had 
its  miraculous  healers  of  disease,  and  each  exponent  has  had  his 
hordes  of  adherents.  Just  as  the  Roman  emperor  Caracalla  wor- 
shipped ApoIIonius  of  Tyana,  who  is  virtually  the  spiritual  pro- 
genitor of  Mary  Baker  Eddy,  so  did  the  nobles  of  mediaeval  times 
bow  before  the  quasi-quackery  of  Paracelsus  and  Mesmer,  and  to- 
day the  devotees  of  various  occult  but  unorthodox  methods  of  heal- 
ing are  numbered  by  legions,  be  they  Christian  Science,  Mental 
Science,  Osteopathy,  or  Chiropraxy. 

And  thus  the  miracles,  so  called,  have  been  in  Of)eration  since 
time  immemorial,  more  often  under  the  guise  of  mystery  than  of 
science,  while  all  the  time  the  fundamental  underlying  factor  lay 
simply  in  a  faith  in  the  power  to  heal,  and  the  influence  of  sug- 
gestion that  makes  for  health,  and  so  the  quasi-religio-medical 
masquerade  has  continued  throughout  the  ages.  Fortunately,  as  in 
other  great  movements,  so  with  these,  the  underlying  germs  of 
truth  lived  on,  until  to-day  psychology  and  rational  medicine  have 
recognised  the  essential  diff"erence  between  organic  and  functional 
disease  and  the  predominance  in  the  symptoms  of  the  functional 
factor. 

Never  has  such  a  stimulus  been  given  to  this  revival  of  interest  in 
the  so-called  occult  healing  as  during  the  present  war,  and  the  vari- 
ous methods  of  curing  functional  disease  have  been  called  to  the  aid  of 
suff'ering  humanity.  Pre-eminent  amongst  these  various  methods  of 
suggestion  there  stands  out  to-day  not  only  the  use  of  hypnotism, 
but  most  of  all  the  employment  of  persuasion,  education,  and  ex- 

1123 


1 124  A  PSYCHO-THERAPEUTIC  CLINIC 

planation.  In  all  the  more  important  warring  countries  neurological 
centres  have  been  established,  which  have  busied  themselves  with 
the  treatment  of  functional  nervous  disorders.  None  of  these  is  more 
impressive  than  that  in  the  Jura  Mountains,  visited  during  the 
summer  of  191 8. 

The  ancient  city  of  Besan^on,  a  capital  city  in  the  time  of  the 
Gauls,  and  known  to  the  Romans  as  Vesontio,  possesses  in  the  Hos- 
pital of  St.  Jacques  a  distributing  centre  for  the  convoys  of  nervous 
cases  brought  from  the  forward  areas  of  the  eastern  battle  zones  of 
France.  Situated  in  the  foot-hills  of  the  Jura  Mountains,  with  its 
picturesque  citadel  built  under  the  direction  of  the  famous  strategist 
Vauban  in  1664,  and  with  its  interesting  ancient  Roman  monuments, 
it  forms  one  of  the  most  delightful  clinical  centres  of  the  war  zones. 
Under  the  skilful  guidance  of  Dr.  Roussy,  soldiers  with  all  manner 
of  nervous  diseases  are  admitted  and  examined,  and  from  this 
"triage,"  or  distributing  centre,  the  functionally  disordered  patients 
are  sent  south  for  treatment  to  the  psycho-therapeutic  centre  at 
Salins.  The  dull  little  town — about  50  kilometres  from  Besan^on, — 
is  reached  by  one  of  the  most  picturesque  roads  in  all  Europe,  and 
the  pilgrimage  thence,  along  the  valleys  of  the  Doubs  and  the 
Loue,  should  bring  one,  in  itself,  a  contentment  of  mind  even  before 
the  destination  is  reached,  viz.:  the  Psycho-therapeutic  Hospital, 
located  in  the  historic  fortress  of  St.  Andre. 

This  well-preserved  monumental  fortress,  2000  feet  above  the 
level  of  the  sea,  likewise  testifies  to  Vauban's  skill,  for  the  fortress 
dominates  the  surrounding  country,  looking  out  upon  the  southern 
and  eastern  borders  of  Switzerland  and  Italy,  a  defence  against 
prospective  invasion  in  the  seventeenth  century.  The  town,  itself, 
with  its  great  salt  beds,  and  its  Etablissement  des  Bains,  erected 
by  Grimaldi  in  1855,  has  been  visited  as  a  health  resort  from 
time  immemorial,  and  to  its  saline  and  sulphur  springs,  as  well 
as  to  its  climate,  have  already  been  attributed  wonderful  healing 
powers. 

One  may  drive  by  a  wide  and  winding  road,  as  do  the  ambu- 
lances, to  the  Fortress  Hospital,  or  one  may  follow  the  example  of 
the  more  energetic  staff  and  climb  the  steep  but  narrow  path, 
leading  by  a  shorter  course,  to  the  mountain  top.  On  arrival  at  the 
Fort  one  crosses  the  moat  by  the  usual  bridge  to  find,  on  entering 


A  PSYCHO-THERAPEUTIC  CLINIC  1125 

the  enclosure,  a  wonderfully  preserved  type  of  fortification  of  the 
reign  of  Louis  XIV:  so  complete  in  its  architectural  design,  and  so 
solid  in  its  structure  as  to  have  been  used  for  its  original  purpose 
down  to  1888,  when  modern  methods  of  warfare  rendered  it  unsuit- 
able for  other  purposes  than  a  garrison.  The  larger  rooms  of  the 
fortress  form  the  wards  of  a  hospital,  while  the  smaller  ones 
are  the  offices,  museums  with  their  exhibits,  and  cinematographic 
shows. 

Nowhere  in  France  is  to  be  seen  such  a  concentration  of  func- 
tional diseases,  nor  will  one  see  anywhere  more  satisfactory  results. 
Paralysis  of  the  extremities  in  all  their  weird  varieties,  hysterical 
paraplegias,  hemiplegias,  and  monoplegias,  soldiers  with  astasia- 
abasia;  others  again  with  contractures  that  have  been  present  for 
years;  some  with  "plicatures,"  their  vertebral  columns  bent  for- 
ward, others  in  a  position  of  scoliosis — some  with  neuropathic 
pseudo-coxalgia,  others  again  with  wry  necks;  and  so  on  ad  infinitum. 
Here,  too,  one  saw  for  the  first  time  the  "Marseilles  thumb,"  an 
adduction,  first  occurring  in  a  soldier  belonging  to  a  regiment  from 
that  ancient  city,  and  later  by  contagion  of  ideas,  occurring  in 
numberless  recruits  from  the  same  source.  Here,  too,  was  seen  the 
obstetrical  hand,  the  mainfigicy  likewise  the  reflex  neuroses,  what- 
ever their  origin,  conditions  ail  cured  more  or  less  speedily  in  quasi- 
miraculous  fashion. 

Not  less  interesting  in  other  wards  were  soldiers  with  unusual 
tremors  and  pseudo-choreic  movements,  resulting  from  emotional 
disturbances  of  war.  The  commoner  psychosensory  disturbances, 
the  defects  of  speech  and  hearing  and  of  sight,  all  of  these  in  varying 
degrees,  were  likewise  amenable  to  the  skilful  treatment  there 
employed. 

And  lastly  is  the  group  of  self-inflicted  lesions — more  especially 
the  extensive  oedemas  resulting  from  ligature — which,  of  course, 
require  treatment  of  an  entirely  diff'erent  character. 

It  is  of  intense  interest  to  note  by  what  methods  Roussy  and  his 
assistants  have  eff"ected  their  cures.  Treatment  by  psychotherapy 
is  too  much  a  matter  of  commonplace  in  every  neurological  centre  of 
Europe  and  England  to  be  dealt  with  here  in  detail.  Suffice  it  to 
say  that  the  methods  diff"er  widely  and  the  approach  to  the  patient 
depends  very  largely  on  the  attitude  of  mind  of  the  physician.  In 


1 126  A  PSYCHO-THERAPEUTIC  CLINIC 

one  clinic  at  Beauvais,  incarceration  in  a  dark  room  under  severe 
privations  was  resorted  to  as  a  disciplinary  measure,  usually  with 
rapid  success.  Patients  who  refused  to  get  well  promptly  were 
returned  to  their  cells  until  such  time  as  the  fear  which  had  induced 
the  disease  was  dominated  by  the  greater  fear  of  its  treatment.  In 
other  clinics,  again,  the  method  of  torpillage  was  adopted  with  signal 
success;  this  consisted  in  the  administration  of  powerful  currents  of 
galvanism,  inasmuch  as,  forsooth,  faradic  electricity  was  not  con- 
sidered sufficiently  severe.  Nevertheless,  in  most  centres  the  less 
drastic,  but  withal  powerful  faradic  brush  has  proved  sufficiently 
efficacious,  and  succeeding  treatments  either  demonstrated  the 
possibility  of  movements  in  disordered  limbs  or,  again,  estab- 
lished a  fear  greater  than  that  which  had  previously  limited  their 
function. 

Still  more  humane  measures  were  adopted  in  many  centres  by 
isolation  in  cubicles,  and  with  milk  diet,  the  object  desired  being 
attained  through  rest  and  discipline.  In  the  Centre  at  Salins,  how- 
ever, these  severe  methods  of  suggestion  and  discipline  are  depre- 
cated, and  the  key-note  of  the  treatment  is  kindness,  persuasion, 
and  education.  New  patients  are  placed  at  rest  in  comfort  for  a  few 
days  after  admission,  and  are  then  allowed  to  circulate  among  those 
whose  cures  are  already  established  or  in  progress,  and  thus  a  con- 
tagion of  health  and  healthy  ideas  is  encouraged;  so  much  so, 
indeed,  that  often  before  the  treatment  is  commenced,  the  need  for 
it  has  almost  disappeared.  Not  infrequently,  indeed,  gentle  faradism 
is  applied,  rather  with  the  object  of  demonstrating  in  contractures 
or  paralysis  that  muscles  are  still  able  to  functionate  and  not  with 
the  idea  of  causing  unnecessary  pain  or  inculcating  discipline.  The 
absence  of  other  means  of  treatment,  of  elaborate  appliances  with 
massage  and  electrical  devices  becomes  very  impressive,  and  it  is 
interesting  to  note  how  at  the  Seale  Hayne  Hospital  in  England,  the 
same  brilliant  success  is  obtained  by  similar  methods  and  along  the 
same  ideal  lines  under  the  skilful  guidance  of  Colonel  Hurst  and  his 
associates.  Here,  as  at  Salins,  the  atmosphere  is  one  of  kindly  interest 
and  rational  therapeutics. 

There  are  many  interesting  demonstrations  of  the  successful 
treatment  at  the  Fortress  hospital  in  the  museums  there  estab- 
lished: the  numberless  crutches,  splints,  and  plaster  appliances, 


A  PSYCHO-THERAPEUTIC  CLINIC  1127 

thrown  aside  because  found  needless,  testify  to  the  importance  of 
proper  diagnosis  and  psycho-therapeutic  treatment. 

A  small  hut  erected  in  the  porter's  grounds  is  devoted  to  the  cine- 
metograph — not  for  the  amusement  of  the  patients,  but  to  demon- 
strate in  a  series  of  graphic  films  the  progress  in  treatment — the 
improvement  in  the  movements  of  affected  hmbs  from  the  inception 
of  the  disease  to  the  period  of  complete  restitution. 

As  in  former  ages  then,  so  to-day  the  performance  of  miracles 
continues,  with  this  difference,  that  this  more  modern  practice, 
while  less  dramatic  though  equally  effective,  is  based  upon  the 
principles  of  science  and  intellectual  honesty. 


THE  LIFE  CHART  AND  THE  OBLIGATION  OF 
SPECIFYING  POSITIVE  DATA  IN  PSYCHOPATH- 
OLOGICAL  DIAGNOSIS 

By  Adolf  Meyer,  M.D.,  Baltimore,  Md. 

IN  his  address  at  the  opening  of  the  Henry  Phipps  Psychiatric 
Clinic,  Sir  William  Osier  told  the  following  charming  anecdote: 
"I  found  a  big  West  Virginian  in  the  private  ward  one  morning. 
The  history  was  colorless.  I  went  over  him  thoroughly.  'There  is 
nothing  the  matter  with  you,'  I  said.  *I  didn't  say  there  was,* 
came  the  reply;  'that  is  what  I  wanted  to  know.'" 

In  quite  a  few  similar  cases  one  might  raise  the  question:  How, 
then,  did  the  patient  come  to  have  doubts  about  his  health?  Many 
a  so-called  neurotic  leaves  the  physician  without  what  really  ought 
to  be  an  obligatory  accounting  for  the  solicitude  or  worry. 

Sir  William  Osier  continues:  "We  are  all  a  bit  sensitive  on  the 
subject  of  our  mental  health,  but  a  yearly  stock-taking  of  psychic 
and  moral  states  under  the  skilled  supervision  of  a  competent 
reviewer  and  interpreter  of  human  problems  and  assets  and  their 
best  management  would  be  most  helpful  to  most  of  us."  He  gives 
a  few  diagnosis  slips: 

"Mr.  J.  A.  A  tendency  to  irritability  of  temper. 

"Mrs.  R.  Too  much  given  to  introspection. 

"Miss  B.  Overanxious  about  her  soul. 

"Master  G.  Worried  by  a  neurasthenic  mother." 

These  are,  indeed,  good  samples  of  problems  presenting  them- 
selves, and  I  feel  that,  if  we  are  able  to  specify  perfectly  objective 
facts  in  terms  of  definite  situations  and  reactions  plainly  inviting 
adjustment  and  action,  there  would  be  little  cause  for  sensitiveness. 

The  two  big  sins  of  the  physician  against  the  psychoneurotic 
are  apt  to  be  the  dismissal  of  the  patient  with,  "Nothing  the 
matter  with  you"  (with  perhaps  a  hint  that  he  or  she  had  best  go 
to  Christian  Science  or  to  some  cure-all),  or  the  statement:  "What 

1 128 


THE   LIFE   CHART  1129 

I  find  is  enough  to  account  for  all  your  nervous  symptoms."  Either 
statement  is  apt  to  encourage  neglect  in  the  examination  of  the 
psychopathological  and  the  situational  status  of  the  patient.  Well- 
directed  attention  to  these  settings  will  make  the  verdict  safer  for 
the  patient,  and  ultimately  also  do  better  justice  to  the  responsi- 
bility of  the  physician. 

How,  then,  can  we  pin  down  the  pertinent  facts?  How  can  we 
get  them  into  a  form  which  will  be  a  safe,  dependable  formulation 
in  terms  of  an  "experiment  of  nature,"  or  of  a  problem  of  functional 
pathology,  suggesting  more  or  less  well-defined  non-derogatory 
therapeutic  modifications? 

Medical  psychology  consists  largely  in  the  determination  of  the 
actual  life-history  and  experiences  and  concrete  reactions  of  the 
patient,  and  the  gaining  of  a  safe  and  sensible  perspective,  so  as 
to  adapt  as  far  as  possible  the  aims  to  the  means  and  the  means 
to  the  aims,  and  the  personality  to  the  situation  and  the  situation 
to  the  personality. 

The  facts  which  really  count  are  as  plain  and  tangible  and 
concrete  and  controllable  as  those  in  any  other  part  of  the  record 
and  examination  of  the  human  being.  Unfortunately,  they  may  be 
unwieldy,  and  form  a  "long  story,"  and  before  we  can  say  that 
we  have  a  clean-cut  and  practically  useful  view  of  the  fateful 
bias  indicated  by  the  history,  it  must  be  shown  by  careful  scrutiny 
of  the  facts  that  the  allegations  tally  with  what  the  person  actually 
shows  objectively  by  behavior  and  associations  and  with  the 
history  furnished  by  the  friends.  It  is  the  length  of  the  records 
and  their  apparent  lack  of  pointedness  that  make  many  physicians 
shun  the  task.  It  is,  furthermore,  somewhat  difficult  to  control  the 
time  relations  and  causal  interdependence  of  the  events. 

To  facilitate  a  concise  final  review  of  the  facts,  I  use  a  device 
which,  I  hope,  illustrates  not  only  our  practice,  but  also  the  entire 
philosophy  involved  in  it. 

The  patient  who  comes  to  the  physician  is  naturally  examined, 
not  only  for  the  history  and  present  condition  of  each  organ  and 
function,  but  also  for  the  development  and  condition  of  the 
integrated  personality.  In  order  to  record  the  facts  in  a  graphic 
manner,  we  can  use  a  life  record  for  each  of  the  principal  organs, 
giving  sufficient  space  for  each  year  so  that  we  can  record  dates 


II30 

Year: 


LIFE   CHART 


Birthday:  Jan.  11. 1895. 


1896 
1897 


Youngest  of  17.    Mother — second  wife. 
Learned  to  walk  and  talk  in  the  first  year. 


Yr. 
1 


Cholera  Infantum 


1898 
1899 
1900 


Broncho-pneumonia 


Croup 


Usual  exanthemata 


1901 
1902 
1903 
1904 
1905 
1906 
1907 
1908 
1909 


Autoerotism  continu- 
ed to  present  (1916} . 


Malaria 


1910 
1911 


1912 
1913 
1914 
1915 


Illicit  relations. 
Nelsser  infection. 


Autoerotism 
increased 


Dq>ression 


1916 
1917 


Well  developed;  large  for  his  age. 


Began  school. 


Open  disposition;  friendly,  but  quiet. 


Pref^red  staying  at  home  to  playing  with  others. 


No  worries. 


Only  close  companion  a  cousin  of  own  age — ^very  wild  b<?y, 
Intimacy  continued  to  present  time  (1916). 


Dredge-hand  in  boat  of  brotber-in-law. 

Left  school  (7th  grade) 


Industrious,  saving  money. 


Bought  boat.    Crabbing, 
dredging  oysters. 


I  Summers  at  home.  Wmters 
\  inBalto.  with  brother. 


Quarrels  with  brothers;  thought  he 
was  abused,  being  the  young^. 


Went  with  girls  often,  but  no  serious  love  affairs. 


Feb. — Refused  admission  to  lodge;  kidney  trouble. 
Depressed;  stopped  work;  worried  over  illness.         At  home. 


Worked  6  weeks.     Uncooscious  in  boat  (Aus.)    Peouliu' 

words  and  behaviour.      Reproached  sisters  for  immorality.        21 

Hears  voices;  uneasy;  frishtened;  then  dull.  At  horn*. 


2 
3 

4 
5 
6 
7 
8 
9 
10 


11 
12 
13 
14 
15 
16 
17 
18 


19 


20 


Development  of  semi-stupor  and  indifference 


Entered  Clinic. 


22 


Fig.  I.  Heredity,  Paternal  Uncle  Alcoholic.  Maternal  Grandfather  Insane. 
One  Brother  had  two  Depressions. 


THE  LIFE  CHART 


1131 


Year: 

,1^ 

Birthday:  May  27,  1885. 

m 

V 

Yr. 

1 

i 

^ 

2 

iim 

3 

•'fill 

4 

1890                                                        1 

■ 

. 

5 

1891 

N    Beginnint;  of  headaches. 

6 

1892                                                       ! 

[  Private  schooL 

7 

1893                                                       1 

/ 

8 

1894                                                      •' 

0 

1895 

'■ 

10 

1896 

••Typhoid" 

1 

> 

11 

1897                                                      • 

C  Sth  grade  repeated. 

12 

1898 

Mcustruatioa  irregular 

■1 

J  Headaches  partly  menstrual,  partly  reactive. 

13 

1899                                                      1 

"^ 

14 

1900 

1 

15 

1901                                                      1 

le 

1902                                                      1 

17 

1903 

1 
t 

Maniage 

18 

1904 

1st  child  died  6  moa.  old. 

1 
1 

19 

1905 

Complications  of  sex-life. 

i 

20 

1906                                                     \ 

- 

31 

1907 

23 

1908                                                     ) 

Indifference  ot  husband T 

Pains  about  the  heart  globus;  d«pre«ion:  exhaustion 

23 

1909 

adchildUveda^^dayi. 

J 

■ 

Growing  invalidisn.    Nnd  of  sympathy. 

24 

1910 

-1 

25 

1911 

3d  child  living. 

26 

1912 

Operation  for  fallen 
stomach.    Appendectomy. 

{ 

Invalidism:  mostly  in  bed.  Call  for  sympathy 
reinforced  by  call  for  operations. 

27 

1913 

Removal  of  owies  and 
tubes. 

Laras*  of  ■totnacb 
by  Dothw  avary  10 
day*  for  3  yaar* 

Eabaiution;  prvMura  is  haad. 
Markad  fatisabUity.  baekaeha. 
paiaa  about  boart.  abouidar  uid 

28 

1914 

Hot  flushes. 

Umba:    Dumbaaw  on  laft  uda: 
aaaaKiTMaaa    to   noiaaa;    poor 
^■laap. 

29 

1915 

In  hospital  from  Feb.  9  to  July  31.  i9«S- 
Beeovery. 

30 

« 
1 

Fig.  2.    Case  of  Invaudism. 


1 132  THE   LIFE   CHART 

at  least  accurately  enough  to  indicate  the  months.  To  give  a 
rational  background  to  the  scheme,  the  weight-curve  of  the  most 
readily  comparable  part  of  each  system  is  charted.  For  the  nervous 
and  mental  conditions  we  use  the  growth  curve  of  the  weight  of  the 
brain;  for  the  respiratory  apparatus,  the  weight-curve  of  the  lungs; 
for  the  circulation,  the  heart;  for  the  digestive  apparatus,  the 
weight-curve  of  the  liver;  and  similarly  we  add  the  curve  of  the 
kidneys  and  that  of  the  thyroid,  thymus,  and  sex  glands.  The 
whole  forms  a  tracing  of  the  life-curve  of  the  entire  organism, 
whose  integration  in  its  relation  to  the  environment  then  becomes 
the  basis  of  the  so-called  "mental  record,**  which  is  entered  in 
terms  of  situations  and  reactions. 

We  begin  with  the  entering  of  date  and  year  of  birth  so  as  to 
be  able  to  read  off  easily  the  individual  age  and  the  corresponding 
calendar  years  (the  age  being  entered  on  the  right  and  the  years 
on  the  left) ;  we  next  enter  the  periods  of  disorders  of  the  various 
organs,  and  after  this  the  data  concerning  the  situations  and 
reactions  of  the  patient.  The  space  on  either  side  of  the  tracing 
of  the  organism  is  used  for  explanations,  but  especially  for  the 
data  which  constitute  the  principal  situations  and  reactions  ex- 
pressing the  "mental**  record,  pjermitting  various  degrees  of  com- 
pleteness. On  the  right  border  near  the  edge  we  may  note  the 
changes  of  habitat,  of  school  entrance,  graduations  or  changes,  or 
failures;  the  various  "jobs**;  the  dates  of  possibly  important 
births  and  deaths  in  the  family,  and  other  fundamentally  important 
environmental  incidents.  Nearer  the  middle  of  the  free  space  to 
the  right  one  enters  the  more  personal  psychobiological  and  prac- 
tical reactions,  such  as  the  beginning  and  development  of  dominant 
interests,  friendships,  etc.;  the  occurrence  of  special  difficulties, 
including  minor  peccadilloes,  such  as  confabulations,  lying,  stealing, 
and  various  temptations,  and  the  duration  of  their  influence. 
Brackets  indicate  the  duration  of  some  of  these  features.  Any 
specific  trends  of  special  importance  in  the  evolution  of  the  illness 
had  best  be  underscored  with  different-colored  inks. 

It  is  well  to  put  on  the  left  side  the  entries  concerning  special 
diseases,  the  sex  fife,  etc.  In  case  that  the  details  of  illnesses  require 
more  space,  certain  periods  can  be  charted  on  a  supplementary 
chart  so  as  to  make  the  spaces  represent  months  instead  of  years. 


THE   LIFE   CHART  1133 

The  two  accompanying  examples  will  explain  the  plan  better 
than  would  extended  description. 

The  first  chart  presents  the  data  of  a  patient  with  schizophrenia. 
The  second  gives  the  facts  in  a  case  of  invalidism  in  which  a  recovery 
might  possibly  have  been  obtained  without  mutilation. 

In  the  latter  case  you  find  from  the  age  of  five  a  habit  of  head- 
aches, a  dependence  on  others,  lack  of  emancipation,  a  tendency 
to  appeal  for  sympathy  by  her  complaints;  then  after  her  marriage 
and  the  birth  of  a  child  and  subsequent  interference  with  her 
normal  instinctive  life,  fear  of  losing  the  aflfection  of  her  husband 
(a  friend  of  the  wife  had  come  to  live  in  the  house),  and  more 
invalidism;  then  several  unfortunate  and  mutilating  operations, 
a  real  evisceration  without  any  evidence  of  a  study  of  the  facts 
in  the  case,  but  finally  a  readjustment  under  a  treatment  re- 
estabhshing  better  habits,  a  better  understanding  of  the  difficulties, 
and  an  end  of  making  the  remaining  organs,  the  stomach  and  the 
head,  the  scapegoats  for  the  failure  of  adaptation. 

This  brief  note  may  illustrate  the  objective  practical  procedure 
of  modern  psychopathological  studies,  and  how  simply,  controllably, 
and  suggestively  the  facts  can  be  brought  into  a  record. 


PNEUMONIA   AND   EMPYEMA   AT   CAMP    DODGE, 

IOWA 

By  Lt.  Col.  Jos.  L.  Miller,  M.C,  Chicago,  III. 

DURING  the  year  preceding  September  20,  1918,  approxi- 
mately 800  cases  of  pneumonia  entered  the  Base  Hospital  at 
Camp  Dodge.  This  does  not  include  upward  of  2000  cases  that 
developed  shortly  after  this  during  the  influenza  epidemic.  These 
pneumonias  may  be  divided  roughly  into  three  groups.  Ordinary 
lobar  pneumonia,  in  all  276  cases  from  September  20,  191 7,  to 
March  20,  1918;  400  streptococci  pneumonias  from  March  20, 
19 1 8,  to  May  10,  191 8;  and  125  lobar  pneumonias  from  May  10, 
19 1 8,  to  September  20,  19 18. 

During  the  autumn  of  191 7  a  very  mild  type  of  pneumonia  prevailed, 
as  indicated  by  a  mortality  of  7  per  cent  in  the  first  100  cases.  During  the 
winter  the  infection  became  more  virulent,  the  mortality  in  the  total  of 
276  cases  being  11.27  per  cent.  In  the  first  88  cases  terminating  by  crisis, 
the  duration  in  7  was  two  days;  in  11,  three  days;  in  13,  four  days;  13, 
five  days;  18,  six  days;  9,  seven  days;  10,  eight  days;  2,  nine  days;  and 
5,  ten  days  or  more.  The  colored  troops,  which  made  up  about  one-sixth  of 
the  strength  of  the  command,  made  up  116  of  the  276  pneumonias. 

The  various  pneumococcus  types  were  as  follows:  I,  22.87  per  cent; 
II,  typical  and  atypical,  46.8  per  cent;  III,  7.6  per  cent;  IV,  22.8  per  cent. 

Inasmuch  as  all  of  the  pneumonia  patients  entered  the  hospital  early, 
while  the  infection  was  still  localized,  and  as  all  were  x-rayed  within  twenty- 
four  hours,  the  lobe  where  the  infection  began  was  quite  accurately  de- 
termined. In  596  cases  of  both  types  where  the  infection  still  was  localized 
the  lower  left  lobe  was  involved  in  253;  lower  right  252;  upF>er  right  45; 
upper  left  23;  middle  13;  entire  right  lung  5;  entire  left  lung  i;  and  in 
both  lungs  5. 

The  lobar  pneumonia  presented  the  usual  symptomatology.  The  only 
point  of  interest  was  the  gradually  increasing  virulence,  as  manifested  by 
the  mortality  from  October  i,  1907,  to  January  i,  191 8,  and  the  gradually 
increasing  frequency  of  empyema.  In  October  this  complication  appeared 
in  2.3  per  cent  of  cases;  in  November,  2.2  per  cent;  in  December,  17.3 

1 134 


PNEUMONIA  AND  EMPYEMA  AT  CAMP  DODGE     1 135 

per  cent,  reaching  its  maximum  in  January  with  27.9  per  cent.  Empyema 
was  further  characterized  by  loculated  pus  pockets,  which  accounted 
for  the  high  mortality.  This  made  diagnosis  extremely  difficult;  although 
the  standing  orders  were  to  have  each  patient  x-rayed  every  five  days  and 
frequent  exploratory  punctures  were  made,  several  patients  came  to 
autopsy  with  undetected  pus  pockets.  The  x-ray,  when  frequently  repeated, 
was  of  considerable  value  in  detecting  an  exudate,  although  the  difi"eren- 
tiation  between  fluid  and  consolidation  was  not  definite.  One  of  the  distinct 
values  of  the  x-ray  was  to  stimulate  careful  physical  examination  by  the 
Ward  Surgeon. 

The  epidemic  of  streptococcus  pneumonia  appeared  suddenly  between 
March  18  and  20,  19 18,  and  continued  with  great  severity  for  six  weeks, 
then  gradually  subsided,  although  the  epidemic  was  not  actually  over 
until  June  i,  19 18.  After  the  first  three  weeks,  however,  the  virulence  of 
the  epidemic  became  less  marked.  This  should  be  emphasized  when  con- 
sidering the  various  therapeutic  measures  employed.  At  the  onset  of  this 
epidemic  it  was  recognized  by  all  the  medical  officers  that  this  was  different 
from  the  pneumonia  they  had  seen  in  civil  life.  Severe  intoxication  app>eared 
very  early,  the  disease  frequently  running  a  very  rapid  course:  Lobar 
dullness  and  lessened  respiratory  sounds  were  the  rule;  but  typical 
bronchial  breathing  was  very  infrequent.  In  addition  to  the  area  specially 
mvolved,  scattered  moist,  fine  rkles  were  frequently  heard  over  various 
parts  of  the  lung.  Rusty  sputum  was  frequent  but  not  constantly  present. 
While  autopsy  revealed  that  we  were  dealing  with  broncho-pneumonia, 
inasmuch  as  the  process  usually  became  confluent  in  one  or  more  lobes, 
from  a  clinical  standpoint,  it  would  have  been  diagnosed  as  lobar 
pneumonia.  Empyema  developed  with  great  frequency  and  was  very 
difficult  to  detect  on  account  of  the  absence  of  bronchial  breathing  and 
the  presence  of  suppressed  breath  sounds  even  in  the  absence  of  fluid. 

Of  the  various  unusual  findings  the  great  frequency  of  empyema  was 
the  most  striking,  as  it  developed  as  a  complication  in  34.8  p>er  cent  of  all 
the  streptococcus  pneumonia.  It  was  most  frequent  in  the  white  troops, 
42  per  cent  as  compared  with  26  p>er  cent  in  the  colored.  Multilocular 
collections  of  pus  were  very  common,  occurring  in  the  interlobar  spaces, 
adjacent  to  the  mediastinum,  posterior  to  the  sternum  and  as  lung  abscesses. 
Suppurative  pericarditis  was  found  in  34.8  per  cent  of  empyemas  coming 
to  autopsy,  or  a  total  of  38  cases.  It  was  associated  with  right-sided 
empyema  11  times,  left-sided  18  times,  and  bilateral  empyema  in  11  cases. 
Suppurative  pericarditis  was  found  only  twice  in  colored  soldiers. 

Suppurative  peritonitis  was  present  in  17  of  the  109  empyemas  coming 
to  autopsy.  The  empyema  was  right  sided  in  8,  left  in  5,  and  bilateral  in  4. 


1 136     PNEUMONIA  AND  EMPYEMA  AT  CAMP  DODGE 

In  6  of  the  17  cases  there  was  a  combination  of  p>eritonitis,  pericarditis, 
and  empyema. 

Other  complications  occurring  with  relative  infrequency  were:  Arthritis 
8  cases  and  erysipelas  5.  Acute  endocarditis  and  gangrene  of  the  lung  was 
found  only  once.  Suppurative  otitis  media  was  quite  common,  but  exact 
figures  are  not  available. 

Empyema  was  much  less  frequent  among  the  colored  soldiers,  develop- 
ing in  only  20  p>er  cent  of  the  cases  as  compared  with  45  per  cent  among 
the  whites. 

The  mortality  of  the  lobar  pneumonias  was  1 1 .2  per  cent,  of  the  strep>- 
tococcus  pneumonias  32.5  per  cent.  The  deaths  from  uncomplicated 
streptococcus  pneumonia  was  10.7  per  cent  in  the  whites,  and  19.9  per 
cent  in  the  colored  soldiers.  The  mortality  of  the  empyemas  occurring 
with  so-called  pneumococcus  pneumonia  was  52.5  p>er  cent.  With  empyema 
occurring  during  the  streptococcus  epidemic  60.4  per  cent.  The  mortality 
was  lower  in  the  colored  soldiers — ^44  per  cent  as  compared  with  64.8  p>er 
cent  among  the  whites. 

The  treatment  of  the  pneumonia,  all  types,  was  fresh  air,  with  mor- 
phine to  relieve  pain  and  give  sleep  and  rest;  tincture  of  digitalis,  beginning 
with  I  c.c.  every  three  hours  day  and  night  at  the  onset  of  the  trouble, 
and  continuing  this  dosage  throughout  the  course  of  the  disease  unless 
evidence  of  intoxication  app>eared.  No  attempt  was  made  to  reduce  tem- 
perature by  bathing.  The  Rockefeller  serum  was  not  used,  and  in  the  276 
cases  of  lobar  pneumonia  only  two  patients  died  from  "type  I"  in- 
fection. 

The  empyemas  developing  as  a  complication  of  the  276  lobar 
pneumonias  were  treated  by  rib  resection.  At  the  onset  of  the  strepto- 
coccus empyema,  immediately  upon  detection  of  a  turbid  fluid  containing 
streptococci,  drainage  under  local  anesthetics  by  rib  resection  was  per- 
formed. The  results  were  not  satisfactory.  Many  patients  returned  from  the 
operating  room  in  a  state  of  shock  from  which  they  did  not  recover.  In 
their  extreme  toxic  condition,  apparently  the  shock  of  the  operation,  and 
especially  the  efi'ect  on  the  heart  of  the  artificial  pneumothorax,  w?5 
sufficient  to  at  least  hasten  a  fatal  termination.  After  employing  this 
method  of  treatment  for  about  ten  days,  a  change  was  made  to  rep)eated 
aspirations  until  the  condition  of  the  patient  was  sufficiently  improved  to 
warrant  operation.  The  results  from  this  procedure  appeared  to  be  much 
better;  in  fact,  the  improvement  was  so  marked  in  some  of  these  cases  after 
a  few  aspirations,  that  the  operation  was  delayed  and  1 1  cases  recovered 
without  operation.  Six  of  these  were  aspirated  only  once.  It  is  possible, 
and  perhaps  probable,  that  these  would  have  recovered  without  aspiration. 


PNEUMONIA  AND  EMPYEMA  AT  CAMP  DODGE     1 137 

When  we  compare  the  mortality  results  of  these  various  methods  of 
treatment,  it  is  noted  that  in  43  cases  with  early  operation,  52.5  per  cent 
died.  In  49  with  repeated  aspiration,  then  operation,  the  mortality  was  32.5 
p>er  cent.  In  56  cases  aspiration  alone  was  performed  either  because  the 
improvement  was  so  marked  after  aspiration  that  an  operation  was  not 
considered  necessary,  or  because  the  patient's  condition  was  so  grave  that 
an  operation  was  unwarranted.  Forty-three,  or  75.7  p>er  cent.,  of  this  group 
died. 

One  point  should  be  considered  in  regard  to  these  figures,  viz. 
that  apparently  the  virulence  of  the  infection  was  more  marked 
early  in  the  epidemic.  Immediate  operative  measures  during  the 
first  three  weeks  of  the  epidemic  gave  a  mortality  of  52.5  per  cent, 
while  immediate  operation  later  in  the  course  of  the  epidemic  gave 
a  mortality  of  28.6  per  cent.  The  difference  in  mortality  from  the 
two  procedures  is  probably  in  part  at  least  only  apparent,  and  can 
to  a  considerable  degree  be  explained  by  the  difi'erence  in  virulence 
at  the  two  periods. 


CLINICAL  OBSERVATIONS  ON  THE  LATE  PULMO- 
NARY EFFECTS  OF  GASSING 

By  Roger  S.  Morris,  M.D.,  Cincinnati,  O. 

Lieutenant  Colonel,  Medical  Corps,  U.  S.  Army,  A.E.F.,  Germany. 

IN  the  Hun's  display  of  frightfulness  during  the  Great  War, 
nothing  which  he  has  exhibited  to  the  civilized  nations  of  the 
world  has  more  clearly  shown  his  utter  lack  of  a  sense  of  honor 
— of  "playing  the  game"  in  a  sportsmanlike  manner — than  his 
treacherous  and  cowardly  introduction  of  poisonous  gases  in  war- 
fare. When  he  launched  this  weapon,  a  new  and  extremely  urgent 
clinical  problem  was  presented  on  a  vast  scale  to  the  Medical  Corps 
of  the  Allied  Armies.  The  situation  was  wholly  unexpected  and 
without  precedent,  and  the  agony  and  suffering  and  the  resultant 
loss  of  Hfe  have  been  untold. 

With  the  acute  effects  of  poisonous  gases  we  need  not  here  con- 
cern ourselves.  It  is  happily  a  closed  chapter,  which,  there  is  every 
reason  to  hope,  will  never  be  reopened.  Unfortunately,  however, 
the  clinical  course  is  frequently  not  ended  with  the  subsidence  of 
the  symptoms  of  acute  poisoning.  It  is  with  the  later  eflFects  of  f>oi- 
sonous  gases  that  the  present  notes  are  concerned. 

It  has  been  pointed  out  by  Professor  Achard,^  in  an  analysis  of 
2218  gassed  cases  (561  of  suffocating  gases,  1657  of  mustard  gas), 
that  suffocating  gases  (chlorine,  phosgene,  etc.)  are  much  more  apt 
to  lead  to  chronic  indispositions  than  is  mustard  gas.  He  found  195 
patients  suffering  from  the  late  effects  of  suffocating  gases.  The 
decision  as  to  the  nature  of  the  gas  was,  however,  often  difficult, 
as  mixtures  of  gases  were  so  frequently  employed.  Among  the 
patients  who  had  been  gassed  with  suffocating  gases,  93  were  ob- 
served within  six  months,  54  within  six  to  twelve  months,  41  be- 
tween one  and  two  years  after  gassing,  and  in  7  the  symptoms  had 
persisted  more  than  two  years.  With  vesicating  gases,  on  the  other 

^  Lecture  delivered  by  Professor  Achard  at  Paris,  October  9,  191 8,  to  members  of 
the  Medical  Corps,  United  States  Army. 

1138 


LATE  PULMONARY  EFFECTS  OF  GASSING       1139 

hand,  there  were  only  3  cases  in  whom  the  symptoms  persisted 
beyond  ten  months. 

As  Professor  Achard  emphasized,  the  symptoms  of  gassed  pa- 
tients are  often  those  of  pulmonary  tuberculosis,  and  it  is  with  this 
group  that  we  are  here  chiefly  concerned.  In  another  connection, 
Thomas  Lewis  and  others  have  also  drawn  attention  to  the  fact  that 
the  eff"ort  syndrome,  in  its  symptomatology,  is  indistinguishable 
from  pulmonary  tuberculosis  and  various  other  organic  diseases.  It 
is  only  by  means  of  objective  examination  that  the  diflFerentiation 
is  possible. 

In  order  to  limit  the  present  communication,  only  those  gassed 
patients  complaining  of  hemoptysis  are  considered.  It  is  here  that 
the  question  of  a  tuberculous  lesion  will  most  frequently  arise.  It 
may  be  added  in  passing  that  the  history  so  frequently  indicated  a 
mixture  of  mustard  gas  with  suff'ocating  gases  that  we  have  not 
attempted  to  diff'erentiate  between  the  two. 

Hemoptysis  has  been  found  to  be  a  relatively  common  late 
symptom  after  gassing.  The  majority  of  our  patients  were  wounded 
with  gas  within  the  last  six  or  eight  months  (February,  19 19),  and 
it  is  not  possible,  from  our  own  observations,  to  state  how  long  this 
symptom  may  persist.  Patients  gassed  at  Chateau-Thierry  in  June, 
19 1 8,  are  still  spitting  up  blood  in  February,  19 19.  It  is  quite  evi- 
dent, from  the  experience  of  the  French,  that  we  will  have  numbers 
of  soldiers  in  whom  the  symptom  may  be  present  months  after 
their  return  home. 

The  amount  of  blood  expectorated  is  generally  small.  Most  fre- 
quently the  sputum  is  only  blood-streaked,  though  at  times  the 
patient  describes  clots  representing  a  teaspoonful  or  more.  In  this 
group  of  patients,  other  symptoms  also  may  strongly  suggest  pul- 
monary tuberculosis.  Chronic  cough  is  common,  usually  worse  in 
the  morning.  There  is  apparently  nothing  characteristic  in  the  ap- 
pearance of  the  sputa.  Night  sweats  are  frequently  complained 
of,  often  so  severe  that  the  clothing  is  saturated  with  moisture. 
Weakness  and  dyspnea  on  exertion  are  almost  always  present, 
greatly  limiting  the  activities  of  the  patient.  Tachycardia  and  pal- 
pitation on  exertion  are  common.  Vertigo  is  not  infrequent.  Among 
our  patients  we  have  encountered  very  few  with  evening  elevations 
of  temperature  to  loi''  F.,  such  as  Achard  describes.  Generally  the 


1 140       LATE  PULMONARY  EFFECTS  OF  GASSING 

temperature  has  been  normal,  or  there  have  been  rises  to  ioo°  or 
less.  Loss  in  weight,  amounting  to  5  to  10  pounds  or  a  httle  more, 
is  common. 

Pain  in  the  chest  has  been  a  frequent  symptom  among  our  pa- 
tients, for  which  it  has  rarely  been  possible  to  detect  a  physical 
basis.  It  is  usually  dull  in  character,  though  occasionally  sharp, 
and  is  nearly  always  produced  or  aggravated  by  deep  inspiration 
or  by  coughing.  A  history  of  preceding  inflammatory  disease  of 
lungs  or  pleura  is  by  no  means  the  rule.  A  recent  patient,  however, 
presented  findings  of  some  interest. 

He  had  had  pneumonia  in  1902  and  was  critically  ill.  A  needle  was 
introduced  into  his  left  axilla  at  that  time,  and  fluid  was  withdrawn.  He 
made  a  complete  recovery  and  was  entirely  well,  except  for  a  second  attack 
of  pneumonia  in  1909,  until  he  was  gassed  last  August.  Since  then  he  has 
suff^ered  with  pain,  dull  in  character,  in  the  lower  left  axilla,  whenever  he 
takes  a  deep  breath.  A  radiogram  shows  a  band  of  adhesions  between  the 
left  chest  wall  and  the  diaphragm;  fluoroscopic  examination  confirms  this 
finding.  Asked,  during  the  latter  examination,  to  indicate  where  he  felt 
pain,  the  patient  placed  his  finger  directly  on  the  point  of  attachment  of 
the  adhesion  to  the  chest  wall. 

The  findings  in  this  patient  suggest  the  p)ossibility  that  similar 
pains  may  be  associated  with  adhesions,  which  escape  detection. 
The  physical  findings  in  the  majority  of  our  patients  have  been 
normal.  That  is,  there  is  not  usually  dullness  or  retraction  of  the 
apices,  and  it  has  been  unusual  to  find  rales,  even  after  cough  and 
deep  inspiration.  In  a  few  instances,  however,  we  have  noted  rales 
persistently  in  one  or  both  apices.  It  is  in  the  patients  with  rales 
and  hemoptysis  particularly  that  pulmonary  tuberculosis  would 
seem  altogether  probable,  and  yet  our  experience,  though  less  ex- 
tensive, coincides  with  that  of  Achard,  in  that  repeated  examina- 
tions of  the  sputa  fail  to  reveal  tubercle  bacilli. 

The  diff'erentiation  of  pulmonary  tuberculosis  and  the  late 
eff'ects  of  gas  is  also  greatly  facilitated  by  x-ray  examination,  as 
Achard  again  has  shown.  One  fails  to  find  the  evidence  of  infiltration 
of  the  lungs  in  gassed  patients.  A  change  which  occurs  with  great 
frequency,  however,  is  an  increase  in  the  density  of  the  hilum 
shadow,  which  tends  to  assume  a  form  more  or  less  oblong.  It  is  not 
pathognomonic,  but  is  very  suggestive  of  gassing. 


LATE  PULMONARY  EFFECTS  OF  GASSING       1141 

There  is  a  smaller  group  of  patients,  of  whom  I  have  seen  only 
a  few  examples,  in  which  the  clinical  picture  is  that  of  advanced 
tuberculosis  of  the  lungs.  Here,  the  patient  is  iller,  there  is  cough 
with  profuse  muco-purulent  or  purulent  expectoration,  frequently 
hemoptysis,  fever  to  102"  to  104°,  with  morning  remissions,  sweats, 
emaciation,  and  great  prostration.  The  clinical  condition  is  pre- 
cisely that  of  advanced  pulmonary  tuberculosis,  and  the  issue  may 
be  fatal  after  a  period  of  months.  Such  a  case  was  seen  on  the  service 
of  Major  J.  B.  Whinnery  at  American  Red  Cross  Military  Hospital 
No.  5  at  Auteuil. 

The  patient,  severely  gassed  in  August,  had  been  confined  to  bed  con- 
tinuously till  his  death  in  November.  The  physical  findings  during  the 
latter  part  of  his  illness  were  those  of  advanced  phthisis  of  both  lungs. 
Repeated  examinations  of  the  sputum  were  negative  for  tubercle  bacilli. 
At  autopsy,  no  evidence  of  pulmonary  tuberculosis  was  found.  There 
were  marked  bronchial  and  peri-bronchial  thickening  and  an  extensive 
acute  broncho-pneumonia,  superimposed  on  a  more  chronic  inflammatory 
process  with  fibrosis. 

The  milder  symptom  complex  is  one  which  will  be  encountered 
frequently  in  civilian  and  military  hospitals  in  Allied  countries. 
The  importance  of  recognizing  its  etiology  and  of  differentiating 
it  from  pulmonary  tuberculosis  is  obvious  from  several  points  of 
view.  In  the  first  place,  the  prognosis  in  the  gassed  patients  is  alto- 
gether good.  The  majority  recover  within  a  year,  according  to 
Achard's  figures;  few  persist  beyond  two  years.  Furthermore,  the 
patient  and  his  family  should  be  spared  the  mental  worry  which 
pertains  to  a  diagnosis  of  tuberculosis. 

From  the  standpoint  of  the  governments  concerned,  the  separa- 
tion of  this  group  of  patients  from  the  tuberculous  is  also  important 
in  relation  ta  pensions,  war  risk  insurance,  etc.  There  is  no  reason 
to  anticipate  at  present  that  the  gassed  patient  will  continue 
indefinitely  to  be  a  burden  upon  the  State,  while  the  reverse  may 
hold  good  in  a  large  percentage  of  the  tuberculous. 

Summarized  briefly,  a  history  of  chronic  cough,  hemoptysis, 
weakness,  sweats,  slight  fever,  loss  in  weight,  in  conjunction  with 
a  history  of  having  been  gassed,  indicates  the  probability  of  a  non- 
tuberculous  condition,  the  result  of  the  gassing.  The  differentiation 
from  tuberculosis  is  made  by  the  absence  of  tubercle  bacilli  from 


1 142       LATE  PULMONARY  EFFECTS  OF  GASSING 

the  sputum  and  by  the  lack  of  jc-ray  evidence  of  tuberculosis. 
Physical  examination  of  the  lungs  may  be  very  suggestive  of  a 
tuberculous  lesion,  and  too  much  importance  should  not  be  attached 
to  persistent  rales.'^ 

*  Owing  to  four  months'  delay  in  transmission,  due  to  faulty  address,  the  invitation 
to  contribute  to  this  volume  was  only  received  February  14,  iQip,  while  stationed  with 
the  Army  of  Occupation  in  Germany.  The  necessity  of  having  the  manuscript  in 
Washington  by  March  20th  has  precluded  the  possibility  of  referring  to  the  literature 
and  has  necessitated  haste  in  preparation.  It  is  felt  that  a  brief  word  of  apology  for 
this  fragmentary,  incomplete  note  is  due,  for  one's  best  would  be  all  too  little  to  offer 
to  the  great  and  beloved  physician,  who  has  given  so  abundantly  to  his  students. — 
R.  S.  M. 


THE    DIAGNOSIS   OF   TRAUMATIC   HEMOTHORAX 
By  Geo.  W.  Norris,  M.D.,  Philadelphia,  Pa. 

IT  would  seem  at  first  sight  that  the  physical  signs  of  traumatic 
hemothorax  or  hemopneumothorax  would  be  identical  with 
those  due  to  pathological  causes.  This,  however,  is  by  no  means 
the  case,  and  hence  it  frequently  happened  during  the  recent  war 
that  erroneous  diagnoses  were  made.  This  article,  which  is  based 
upon  the  personal  observation  of  many  hundred  penetrating  or 
perforating  wounds  of  the  chest,  is  written  with  the  object  of  setting 
forth  what  appear  to  the  author  to  be  the  most  important  points 
to  be  borne  in  mind.  In  order  intelligently  to  interpret  physical 
signs  it  is  necessary  to  form  a  mental  picture  of  conditions  within 
the  chest.  Some  of  the  possibilities  may  be  mentioned. 

1 .  A  high- velocity  bullet  may  have  perforated  the  chest,  causing 
only  minute  wounds  of  entrance  and  exit,  associated  with  but  little 
bleeding,  pneumothorax,  or  pulmonary  collapse. 

2.  A  shell  fragment  may  be  lodged  in  the  lung,  which  has  bled 
profusely  into  the  pleural  cavity;  (a)  there  may  be  free  air,  free 
blood  and  a  collapsed  lung;  or  (6)  there  may  be  httle  or  no  free  air, 
a  large  hemothorax  and  a  compressed  lung,  the  latter  being  Nature's 
usual  method  of  checking  hemorrhage. 

3.  The  superficial  wound  may  be  large,  with  extensive  commi- 
nution of  the  ribs,  and  the  wound  of  the  (air)  "sucking"  variety. 
This  type  being  usually  associated  with  marked  mediastinal  dis- 
placement, dyspnea,  shock,  and  ultimately,  if  the  patient  survives, 
infection. 

It  is  well  to  remember  that  in  all  three  types  the  diaphragm  is 
always  high  even  when  considerable  blood  has  flowed  into  the 
pleural  cavity.  There  are  thus  always  four  possible  causes  for 
tympany  on  percussion,  which  is  a  very  frequent  finding;  i.e.  (o), 
free  air,  (6)  relaxed  lung,  (c)  high  abdominal  viscera,  (d)  gas  bacillus 
infection. 

"43 


1 144    DIAGNOSIS  OF  TRAUMATIC  HEMOTHORAX 

Mediastinal  displacement  is  very  common,  and  it  is  particularly 
to  be  emphasized  that  abnormal  physical  signs  on  the  uninjured 
side,  especially  posteriorly,  are  of  very  frequent  occurrence.  The 
mistake  most  commonly  made  by  the  novice  is  to  diagnosticate  a 
pneumonia  either  on  the  wounded  or  unwounded  side,  when  none 
exists.  Pneumonia  as  a  complication,  esp>ecially  an  early  complica- 
tion, is  unusual,  not  to  say  rare;  whereas  the  physical  signs  of  pneu- 
monia are  quite  common.  The  presence  of  fever  and  leucocytosis  is 
of  little  aid  in  diflFerentiation,  as  they  may  readily  be  due  to  wound 
infection. 

As  in  civil  practice,  it  is  usually  impossible  to  demonstrate  by 
physical  signs  a  pleural  effusion  of  less  than  400  c.c.  The  x-ray  is 
often  equally  useless  as  a  diagnostic  aid  for  small  effusions,  espe- 
cially if  the  patient  is  on  his  back. 

Hemothorax  with  or  without  atelectasis  either  on  the  injured  or 
the  opposite  side  may  exist  without  actual  penetration  of  a  missile. 

I.  The  History.  A  man  whose  lung  has  been  wounded  usually 
falls  to  the  ground,  frequently  suffers  from  immediate  severe  dysp- 
nea, and  as  a  rule  either  at  once  or  within  a  short  time  spits  up  blood. 
The  mere  fact  that  he  was  able  to  walk  or  crawl  a  mile  or  more 
(usually  with  frequent  halts)  is  no  indication  that  he  has  not  suffered 
severe  pulmonary  damage. 

II.  Inspection.  Dyspnea  of  varying  degree,  with  unilateral 
diminution  of  thoracic  movement,  often  associated  with  pallor  and 
bloody  expectoration,  are  the  usual  phenomena.  If  the  lesion  is 
right-sided,  a  visible  displacement  of  the  cardiac  impulse  is  the  most 
striking  and  diagnostically  important  feature,  indicating  not  only 
a  pleural  effusion,  but  suggesting  a  considerable  amount.  It  must 
not  be  forgotten,  however,  the  left-sided  pulmonary  collapse,  which 
may  be  contralateral,  and  which  may  occur  simply  from  contusion 
without  penetration,  may  be  deceptive.  Such  collapse,  although  rare, 
has  been  demonstrated  both  radiographically  and  at  autopsy.  Con- 
tralateral atelectasis  must  not,  however,  be  invoked  to  explain 
physical  signs  unless  other  causes  can  be  eliminated  with  reasonable 
certainty.  Cardiac  displacement  to  the  right  from  a  left-sided  hemo- 
or  hemopneumothorax  is  less  easy  to  determine  by  inspection  of 
the  cardiac  impulse  alone,  although  diminished  respiratory  motion 
is  usually  found. 


DIAGNOSIS  OF  TRAUMATIC  HEMOTHORAX     1145 

III.  Palpation.  Except  as  an  aid  in  locating  the  position  of  the 
heart,  palpation  has  usually  less  value  than  the  other  classical 
methods  of  examination.  As  a  rule  fremitus  is  diminished  over  the 
effusion  and  increased  over  the  unaffected  side.  If  the  lung  behind 
the  effusion  is  markedly  compressed,  fremitus  will  be  present,  as 
is  the  case  in  the  pathological  effusions  of  civil  practice. 

IV.  Percussion.  The  frequent  occurrence  of  tympany,  and  the 
possible  causes  thereof,  have  already  been  pointed  out.  Such  tym- 
pany is  usually  quite  readily  differentiable  from  the  hyper-resonance 
encountered  over  the  sound,  vicariously  functionating  side.  Quite 
often,  esp>ecially  if  the  patient  has  been  lying  on  his  back,  the  whole 
anterior  and  lateral  aspects  of  the  chest  may  be  tympanitic  and 
only  posteriorly  will  dullness  be  demonstrable.  It  is  often  quite  im- 
possible to  outline  the  cardiac  dullness  on  one  or  the  other  side  owing 
to  the  presence  of  such  tympany.  Not  infrequently  Grocco's  area 
of  triangular  dullness  can  be  demonstrated,  especially  in  large  hemo- 
thoraces.  Frequently  this  will  be  associated  with  bronchial  breathing 
on  the  uninjured  side,  a  physical  sign  which  may  result  from  medi- 
astinal displacement,  either  with  or  without  compression  of  the 
sound  lung.  Such  bronchial  breathing  is  often  mistaken  for  pneu- 
monic consolidation.  Movable  dullness  is  sometimes  demonstrable, 
especially  if  free  air  is  present,  but  as  a  rule  the  blood  is  too  clotted, 
and  the  pleural  cavity  too  full  of  blood  and  lung  to  permit  of  much, 
or  of  a  rapid  gravitation  of  blood.  Nor  is  the  demonstration  of  mov- 
able dullness  worth  the  trouble  its  demonstration  entails. 

V.  Auscultation.  Associated  with  the  increased  respiratory  ex- 
cursion which  one  sees  on  the  sound  side,  the  breath  sounds  are 
harsh,  exaggerated,  and  variably  associated  with  rales.  The  sounds 
are  often  so  loud  that  they  are  transmitted  to  the  injured  side,  where, 
especially  below  the  clavicle,  they  may  give  the  impression  that  the 
upper  lobe  is  functioning,  whereas  this  lung  may  be  atelectatic  or 
completely  compressed.  When  in  doubt  in  this  regard,  the  degree  of 
motion  of  the  injured  side  and  the  amount  of  cardiac  displacement 
will  often  make  the  situation  clear.  Bronchial  breathing,  whether 
heard  over  the  sound  or  the  injured  side,  will  nearly  always  indicate 
compression,  and  but  rarely  pneumonic  consolidation.  Amphoric 
or  cavernous  breath  sounds,  generally  associated  with  whisp>ered 
pectoriloquy,  point  to  hemopneumothorax  and  are  often  heard  over 


1 146    DIAGNOSIS  OF  TRAUMATIC  HEMOTHORAX 

chests  with  sucking  wounds  or  after  drainage  tubes  have  been  in- 
troduced. 

Friction  sounds  are  generally  present  and  result  from  the  sticky 
fibrinous  moiety  of  the  outpoured  intra-pleural  blood.  The  testing 
of  vocal  resonance  by  means  of  whispering  is  preferable  to  speaking, 
inasmuch  as  it  is  less  taxing  to  the  patient. 

VI.  Exploration.  A  good-sized  exploratory  needle  and  a  reliable 
syringe  should  be  unhesitatingly,  freely,  and  repeatedly  used,  not 
only  for  the  purpose  of  demonstrating  a  hemothorax — which,  if 
small,  is  of  minor  importance — but  of  determining  the  presence  of 
infection,  especially  infection  by  a  gas-producing  organism.  It  is  to 
infection  that  practically  all  the  late  fatalities  are  due.  One  must 
bear  in  mind  that  infection  is  often  localized,  and  that  although  a 
single  exploration  may  yield  a  sterile  culture,  another  puncture 
only  a  few  inches  away  may  reveal  virulent  organisms.  As  a  rule  the 
blood  contained  in  the  pleural  sac  is  clotted,  and  needling  at  the 
angle  of  the  scapula  often  yields  a  "dry  tap"  at  a  time  when  large 
quantities  of  liquid  blood  can  be  withdrawn  high  up,  anteriorly  or 
in  the  anterior  axillary  line.  The  high  position  of  the  diaphragm 
which  has  already  been  alluded  to  must  be  borne  in  mind  when 
exploratory  punctures  are  made. 

When  blood  has  been  poured  out  into  the  pleural  cavity,  it 
after  a  time  separates  into  two  parts:  (a)  a  thick,  fibrinous  cor- 
puscle-enmeshing portion  which  accumulates  posteriorly,  especially 
at  the  base;  takes  a  long  time  to  absorb;  forms  adhesions;  and 
is  accountable  for  the  persistent  percussion  dullness  which  lasts 
long  past  the  usual  convalescent  period;  and  (6)  a  thin,  dark-red 
or  brownish-red  fluid,  which  collects  anteriorly  and  laterally,  and 
constitutes  the  "blood"  which  is  withdrawn  when  aspiration  is 
performed. 

It  is  usually  advisable  on  the  third  or  fourth  day  after  the  in- 
jury to  remove  as  much  of  the  outpoured  blood  as  possible.  Sec- 
ondary hemorrhage  is  usually  small  in  amount,  and  the  removal 
of  large  eff"usions  markedly  shortens  the  period  of  convalescence, 
and  gives  great  mechanical  relief  to  the  respiratory  and  cardio- 
vascular functions. 

Injected  Hemothorax.  The  chief  function  of  the  physician  in  such 
cases  as  have  been  discussed  lies  in  the  early  detection  of  infection. 


DIAGNOSIS  OF  TRAUMATIC  HEMOTHORAX     1147 

If  infection  can  be  avoided,  the  vast  majority  of  patients  who  reach 
the  Evacuation  Hospital  will  ultimately  recover. 

A  persistent  or  increasing  temperature  or  pulse  rate  are  the  most 
reliable  indices  of  an  infected  hemothorax.  The  possibility  of  its 
loculation  and  the  importance  of  frequent  needling  have  already 
been  alluded  to.  Constitutional  signs  such  as  anorexia,  restlessness, 
increasing  pallor,  insomnia,  are  important  signs  but  usually  rather 
late  manifestations.  A  sudden  increase  in  tympany,  cardiac  displace- 
ment, and  the  appearance  of  (often  deep)  jaundice  point  strongly 
toward  gas  bacillus  infection  and  indicate  immediate  resection  and 
drainage. 

A  pK)int  which  is  often  perplexing,  of  which  the  solution  is  chiefly 
a  matter  of  individual  judgment  and  experience,  is  the  decision  to 
operate  or  not  to  operate  against  the  dictates  of  bacteriological 
findings.  Not  infrequently  a  patient  will  show  steady  improvement, 
absence  of  constitutional  symptoms,  and  a  practically  normal  or 
constantly  declining  pulse  rate  and  temperature,  while  the  labora- 
tory reports  organisms  microscopically  or  growth  on  culture  media. 
In  such  cases  it  is  often  best  to  wait  further  developments,  remem- 
bering that  the  infected  area  may  be  walled  off"  and  that  recovery 
may  take  place  without  having  to  subject  the  patient  to  the  pro- 
longed and  trying  convalescence  which  a  thoracotomy  entails.  If 
such  a  course  is  pursued  the  patient  must  be  assiduously  watched, 
and  the  physician  should  be  fully  aware  of  the  resp)onsibility  he 
has  assumed.  This  applies,  although  with  great  rarity,  to  cases  in 
which  gas-producing  organisms  have  been  reported.  As  a  rule,  how- 
ever, the  presence  of  a  gas  bacillus  is  an  absolute  indication  for 
immediate  operation.  There  are,  on  the  other  hand,  cases  in  which, 
despite  negative  bacteriological  findings,  rib  resection  should  be 
performed.  A  fetid  odor  of  the  aspirated  blood  also  points  most 
emphatically  to  surgical  intervention,  but  one  must  not  be  misled 
by  the  stale,  mawkish  odor  which  old  blood  often  possesses  even 
when  it  is  culturally  quite  sterile  and  innocuous.  After  all  is  said 
and  done  one's  decision  will  be  markedly  influenced  by  the  confidence 
one  has  in  one's  bacteriologist. 

Abdominal  Signs  and  Symptoms.  Injuries  of  the  pleura,  especially 
when  in  the  neighborhood  of  the  diaphragm,  often  give  rise  not 
only  to  abdominal  pain  and  rigidity,  but  also  to  nausea  and  vomiting. 


1 148    DIAGNOSIS  OF  TRAUMATIC  HEMOTHORAX 

These  facts  are  important  for  the  obvious  reason  that  one  frequently 
has  to  decide  whether  the  missile  which  entered  the  pleura  has  pene- 
trated the  diaphragm,  perforated  a  viscus,  or  set  up  a  peritonitis. 
Needless  anesthetization,  especially  with  ether,  of  a  man  who 
already  has  a  wounded  lung  is  of  course  most  reprehensible. 

The  occurrence  of  jaundice  may  also  lead  to  diagnostic  difficulty. 
It  may  be  due  to  hepatic  injury,  but  it  may  also — at  times  appearing 
with  great  intensity  and  rapidity — be  due  to  gas  bacillus  infection  of 
the  pleura  when  no  subdiaphragmatic  injury  has  occurred. 

X-ray  Examination.  An  x-ray  examination  of  every  case  is 
essential  to  determine  the  presence,  size,  shape,  and  location  of  the 
missile.  It  is  also  useful  as  a  means  of  corroboration  of  one's  physical 
diagnosis.  Mediastinal  displacement,  pulmonary  collapse,  free  air  or 
blood  in  the  pleural  cavity  are  readily  demonstrabfe,  and  at  times  a 
pus  collection  can  be  located  which  would  otherwise  be  sought  for 
in  vain.  Short  exposures  and  stereoscopic  plates  are  very  necessary. 

The  Uninjured  Side.  It  is  often  more  important  carefully  to 
determine  the  condition  of  the  sound  than  of  the  injured  lung. 
Upon  the  functioning  of  the  uninjured  lung  the  patient's  life,  at 
least  for  a  time,  almost  entirety  depends.  The  frequency  with  which 
signs  of  consolidation — which  disappear  after  aspiration — are  met 
with  has  been  alluded  to.  One  should  always  ask  oneself:  "How 
many  lobes  are  functioning?" 

It  is  remarkable  in  how  many  different  directions  and  from  what 
variable  angles  a  lung  may  be  traversed  by  a  rifle  or  machine-gun 
bullet  without  doing  any  permanent  damage.  Small  lodged  shell 
fragments  may  be  almost  equally  innocuous,  but  in  the  latter 
instance  the  danger  of  subsequent  infection  is  much  greater.  In  ail 
cases,  careful  and  prolonged  observation  and  the  avoidance  of 
meddlesome  surgery  should  be  the  keynotes  of  treatment. 


THE  PERITONEAL  SYNDROME  IN  MALARIA 
By  H.  C.  Parsons,  Lt.  Col.  CA.M.C,  Toronto,  Ont. 

THIS  is  the  term  applied  by  recent  writers  to  the  acute 
abdominal  symptoms  arising  in  the  course  of  malaria.  The 
picture  of  an  acute  abdominal  accident  is  so  clearly  drawn 
that  cases  have  been  admitted  to  hospital  as  surgical  emergencies, 
with  diagnosis  of  appendicitis,  intestinal  perforation,  gall  stones, 
perforation  of  gastric  ulcer,  pyosalpinx,  and  even  ruptured  ectopic 
gestation.  Laveran  referred  to  it  as  "Malaria  with  symptoms  of 
peritonitis,"  and  speaks  of  the  vomiting,  severe  abdominal  pain,  and 
distension.  The  literature  of  this  condition  is  very  scant.  I  am  able  to 
find  only  four  references  with  dates  from  1900  to  1905.  The  most 
recent  treatise,  that  by  Armand-Delille,  Abrami,  Paisseau,  and 
Lemaire  on  the  "Malaria  in  Macedonia,"  observations  made  during 
the  period  of  occupation  by  the  Allied  armies,  gives  it  only  a  brief 
note.  I  find  no  reference  to  it  in  the  Johns  Hopkins  Hospital  Reports 
1895  (Thayer  and  Hewitson),  nor  in  Thayer's  "Lectures  on  Malaria," 
1897,  and  I  do  not  recall  an  instance  while  at  Johns  Hopkins  Hos- 
pital, when  it  was  my  privilege  to  act  as  house  physician  to  Professor 
Osier. 

The  malaria  which  we  saw  in  Macedonia  from  19 15  to  19 17 
was  unusual  both  in  extent  and  severity;  the  clinical  manifesta- 
tions were  most  varied,  and  the  syndromes  corresponded  to  every 
system,  cardio-vascular,  respiratory,  nervous,  genito-urinary,  ocular, 
gastro-intestinal,  peritoneal,  and  the  organs  of  internal  secretion. 

It  is  the  peritoneal  syndrome  to  which  I  would  draw  attention. 

Pain  in  the  abdomen  was  an  almost  constant  complaint  of  sol- 
diers admitted  to  hospital  suffering  from  malaria.  Vomiting,  pain  in 
the  head,  stomach,  back,  and  legs  was  the  usual  formula,  varying 
from  a  dragging  sensation  to  acute  pain.  It  was  first  felt  in  the  left 
hypochondrium,  and  was  found  to  be  associated  with  an  enlarged 
and  tender  spleen;  at  times  there  was  a  noticeable  muscle  spasm 
in  this  region.  In  the  majority  of  cases  this  was  a  transient  affair. 

1149 


1 150     THE  PERITONEAL  SYNDROME  IN  MALARIA 

In  more  marked  cases  there  was  an  extension  toward  the  middle 
line,  the  upper  abdominal  zone  being  the  seat  of  pain,  tenderness,  and 
rigidity. 

In  the  still  more  marked  form  there  was  general  abdominal  pain, 
the  whole  abdomen  was  tender  on  pressure,  there  was  some  disten- 
sion, and  the  muscle  spasm  was  most  striking.  In  some  instances 
these  signs  were  distinctly  localized,  the  right  side  showing  marked 
rigidity  as  compared  with  the  left,  and  in  several  cases  the  right 
iliac  fossa  was  rigid  while  the  rest  of  the  abdomen  was  soft,  the 
picture  of  an  acute  appendix;  or  the  upper  right  quadrant  might  be 
involved,  simulating  an  acute  gall-bladder  infection. 

The  following  cases  quoted  from  the  literature  will  illustrate  these 
points:  Gillot  (i)  cites  the  case  of  a  woman  admitted  to  hospital  at 
Algiers  in  a  typhoid  state,  supposedly  enteric  fever.  She  remained 
in  this  condition  for  several  days,  when  acute  abdominal  symptoms 
suddenly  appeared.  Intestinal  perforation  was  suspected  and  lap- 
arotomy was  performed.  Nothing  abnormal  was  found,  no  typhoid 
lesions,  no  perforation;  it  was  later  found  to  be  a  case  of  malaria. 

He  reports  two  other  cases  of  malaria  with  acute  abdominal 
symptoms,  one  with  marked  localization  in  the  right  iliac  fossa. 

Soulie  relates  the  case  of  a  male  forty-four  years  of  age,  with 
fever  and  rose  spots,  acute  abdominal  symptoms  developed.  Opera- 
tion was  advised,  but  the  finding  of  the  benign  tertian  organism 
in  the  blood  revealed  the  true  nature  of  the  case. 

In  these  reports  no  mention  is  made  of  the  leucocyte  count. 

Jackson  (2)  reports  these  cases: 

(i)  Fever,  chills,  and  sweating,  with  pain,  at  first  in  the  upper  abdomi- 
nal zone,  and  later  in  the  lower.  The  spleen  was  enlarged.  The  malarial 
parasite  was  found,  leucocytes  8900  per  c.mm. 

(2)  Diagnosis  of  pelvic  peritonitis,  with  pain,  tenderness,  and  resistance 
in  the  right  iliac  fossa.  The  spleen  was  enlarged.  The  malarial  parasites 
were  found,  leucocytes  5100  per  c.mm. 

(3)  A  case  with  repeated  attacks  of  malaria  and  acute  epigastric  pain 
with  each  recurrence.  After  the  subsidence  of  the  fever  marked  epigastric 
tenderness  persisted  for  some  days. 

Capps  (3)  reports  the  following: 

(i)  Diagnosis  of  acute  salpingitis.  Chills  and  fever,  to  103**  daily.      ' 


THE  PERITONEAL  SYNDROME  IN  MALARIA      1151 

The  spleen  was  palpable.  There  was  acute  abdominal  pain  mostly  in  the 
lower  zone.  Leucocytes  5800. 

(2)  For  six  days  patient  had  fever,  headache,  vomiting,  and  pain  in 
the  epigastrium  so  acute  as  to  require  morphia;  admitted  to  hospital  as  a 
surgical  emergency  with  a  provisional  diagnosis  of  gall  stones,  or  perfor- 
ating gastric  ulcer.  The  spleen  was  palpable.  Leucocytes  8900;  this  was 
considered  evidence  against  peritonitis.  Malaria  parasites  were  found. 

(3)  Female,  with  a  history  of  former  pelvic  trouble,  chills  and  fever, 
but  no  pain  at  first.  Later  cramplike  pain  in  abdomen  and  later  localized 
pain  right  iliac  fossa,  so  severe  that  she  fainted.  Spleen  palpable,  abdomen 
tender  and  resistant  over  right  iliac  fossa.  Pelvis  showed  lacerated  cervix 
and  mass  in  left  ovarian  region,  not  tender.  Extra-uterine  pregnancy 
diagnosed,  and  brought  to  hospital  for  immediate  operation.  W.B.C.  5000. 
The  benign  tertian  parasites  were  found. 

(4)  Diagnosis  Appendicitis.  Diarrhoea  and  cramplike  pains  in  lower 
abdominal  region  on  left  side,  vomiting.  Subsequently  with  a  chill,  there 
was  severe  abdominal  pain  localised  in  right  iliac  fossa.  Pain  less  between 
chills  but  renewed  with  them.  W.B.C.  3000.  Malarial  parasites  found. 

The  following  cases  will  picture  the  condition  as  we  saw  it. 

Case  I.  Private  H.,  age  twenty-five,  was  admitted  to  No.  4  Canadian 
General  Hospital  at  Salonica  on  July  10,  1916,  with  a  tentative  diagnosis 
of  malaria.  On  examination  the  spleen  was  found  to  be  enlarged  and 
tender  and  there  was  marked  tenderness  in  the  left  hypochondrium. 

July  1 2th.  Patient  complains  of  acute  abdominal  pain;  this  is  general- 
ised. There  is  marked  rigidity  over  the  entire  abdomen,  also  great  tender- 
ness; there  is  no  distension.  Leucocyte  count  8800  per  c.mm. 

Twelve  hours  later  leucocytes  are  18,000,  the  pain  and  rigidity  jjersist 
more  or  less  generally,  but  more  marked  in  right  iliac  fossa.  In  view  of  this 
localisation  of  signs,  and  the  rapid  rise  in  the  leucocyte  count,  the 
abdomen  was  opened.  Nothing  abnormal  was  found.  The  appendix  was 
free  from  disease  and  the  apF>earance  of  the  peritoneum  was  normal. 

The  day  after  the  operation  the  patient  had  a  chill,  temperature  rising 
to  104".  The  following  day  another  chiil  with  temperature  of  103*.  Blood 
examination  showed  the  benign  tertian  parasite.  Under  quinine  recovery 
was  rapid  and  complete. 

Case  II.  Cpl.  B.,  age  twenty-four.  Malaria.  The  onset  was  two  weeks 
ago,  with  severe  headache,  vomiting,  chills,  sweats,  and  general  weakness. 
He  had  had  no  preventive  quinine.  Reported  sick  at  Kukush,  July  21,  1916. 
Admitted  to  28  CCS.  with  temperature  of  104.6°  and  was  given  quinine. 

July  25th.  On  admission  to  No.  4  Canadian  General  Hospital  the 


1 152      THE  PERITONEAL  SYNDROME  IN  MALARIA 

temp>erature  was  normal,  herpes  on  lips,  tongue  clean  and  moist,  heart 
and  lungs  clear,  spleen  soft  and  palpable,  abdomen  slightly  rigid.  Tertian 
parasite  in  the  blood. 

July  31st.  Has  a  severe  diarrhoea,  temperature  101°,  pulse  rapid,  stools 
negative  for  dysentery  group. 

August  2d.  Diarrhoea  ceased,  temperature  99",  pulse  98,  markedly 
dicrotic.  Patient  complains  of  pain  in  epigastrium  and  left  hypochondrium, 
abdominal  respiration  somewhat  restricted,  no  distension;  there  is  general 
rigidity,  both  recti  very  firm,  the  right  more  than  the  left,  the  hypo- 
gastrium  very  rigid  and  boardlike  but  resonant  on  percussion,  spleen  still 
palpable  and  very  tender.  Leucocytes  12,000. 

August  3d.  Leucocytes  14,000. 

The  abdominal  signs  and  leucocytosis  of  14,000  persisted  for  seven  days. 

August  13th.  Tenderness  and  rigidity  gone. 

Case  III.  Private  Hg.  Admitted  to  No.  4  Canadian  General  Hospital, 
September  12,  191 6.  Diagnosis  malaria.  Benign  tertian  parasite  found 
in  the  blood.  Temperature  103**.  He  complains  of  pain  in  abdomen;  on 
examination  there  is  marked  tenderness  and  rigidity  and  some  distension. 
Enlargement  of  the  spleen  is  doubtful.  Leucocytes  7000. 

September  13th.  Symptoms  and  signs  as  before,  leucocytes  14,000. 

The  leucocytosis  persisted  until  September  i6th.  Pain  and  rigidity 
lasted  until  September  20th. 

Case  IV.  Driver  H.,  age  thirty.  Diagnosis  malaria,  second  attack. 
Patient  had  been  in  the  Struma  Valley  seven  weeks,  and  had  been  taking 
preventive  quinine.  First  attack  in  July.  He  was  in  the  28th  General 
Hospital  three  weeks  and  returned  to  duty  August  i  ith. 

Reported  sick  September  i6th,  with  "pain  in  head,  back,  legs  and 
stomach."  Chills  and  fever,  diarrhoea,  no  vomiting.  September  22d, 
admitted  to  No.  4  Canadian  General  Hospital.  Temperature  103°.  Gen- 
eral condition  fairly  good,  tongue  furred.  Heart,  soft  systolic  bruit  at  apex, 
transmitted  a  short  distance  to  the  left.  Apex  is  within  mammary  line. 
Lungs,  coarse,  dry  riles  over  left  side.  Abdomen,  full,  tense,  and  tender, 
some  rigidity,  more  so  on  the  right  side.  Spleen  easily  felt  and  vjery  tender. 
He  is  taking  quinine,  40  grains  daily. 

September  23d.  Temperature  normal,  abdominal  pain  severe,  general 
tenderness  and  rigidity,  more  in  the  upper  zone,  but  to  less  extent  in  the 
lower.  Leucocytes  13,000. 

September  25th.  Distension  marked,  rigidity  general,  tenderness  more 
marked  over  splenic  region.  This  condition  persisted  until  the  29th. 

In  this  case  the  malarial  organism  was  not  found.  The  difficulty  of 
demonstrating  it  in  a  case  where  quinine  has  been  taken  for  a  long  period 


i 


THE  PERITONEAL  SYNDROME  IN  MALARIA      1153 

of  time  is  well  known.  There  is  no  doubt  as  to  the  nature  of  the  case  from 
history  and  clinical  findings. 

Case  V.  Private  McC,  age  forty-seven.  Diagnosis  malaria  (benign 
tertian).  Patient  had  been  on  the  Struma  front  for  six  months,  and  had 
taken  quinine  regularly.  This  is  the  first  attack  of  malaria.  He  reported 
sick  December  14,  1916,  with  pain  in  left  side,  headache,  "shivers,"  fever, 
vomiting,  and  shortness  of  breath. 

December  17th,  admitted  to  No.  4  Canadian  General  Hospital.  On 
examination,  general  condition  fair,  temperature  98**,  tongue  clear,  heart 
and  lungs  clear.  Complains  of  acute  pain  in  lower  left  axilla.  There  is 
great  tenderness  over  left  side  of  abdomen  and  splenic  area,  and  rigidity 
of  the  left  rectus  muscle,  spleen  enlarged,  palpable,  and  tender.  The  benign 
tertian  parasite  is  found. 

December  19th.  Marked  rigidity  of  left  side  of  abdomen,  more  so  in 
the  upper  part  and  extending  across  the  epigastrium  to  the  middle  line. 
Left  rectus  much  firmer  than  right.  On  deep  inspiration  spleen  is  palpable  and 
very  tender.  There  is  no  cough;  left  side  of  chest  clear;  no  signs  of  pleurisy. 

December  iid.  There  is  still  a  little  rigidity  in  the  upper  left  quadrant 
of  the  abdomen.  Spleen  still  palpable.  Left  side  of  chest  clear.  No  report 
of  leucocyte  count  in  this  case. 

It  will  be  noted  that  while  the  abdominal  signs  in  these  cases 
were  in  the  first  place  generalised,  there  was  later  a  localisation 
which  gave  rise  to  a  striking  mimicry  of  a  local  condition. 

Regarding  the  leucocytosis  Jackson  and  Capps  state  that  it 
does  not  occur,  and  hold  that  its  absence  is  a  p>oint  of  differentiation 
from  peritonitis.  In  this  I  cannot  agree.  The  four  cases  in  this 
series  in  which  the  count  was  made  all  showed  a  leucocytosis,  it 
moreover  was  of  the  inflammatory  type,  with  a  relative  increase  or 
the  polynuclear  elements. 

Again  its  appearance  was  sudden  and  corresponded  to  the 
increase  in  the  acuteness  of  the  clinical  signs;  in  Case  I,  in  twelve 
hours;  and  in  Case  III,  in  twenty-four  hours. 

This  is  precisely  what  happens  in  a  perforation  of  an  intestine, 
or  a  rupture  of  an  appendix.  Itwould  appear,  then, that  the  presence 
or  absence  of  a  leucocytosis  has  not  the  value  that  has  been  accorded 
to  it  for  the  purf>oses  of  diff"erentiation. 

The  two  points  of  real  value  are  the  presence  of  an  enlarged 
spleen  and  the  malarial  parasite  in  the  blood  smear. 

In  Case  I  the  indications  for  surgical  interference  were  clear. 


1 154     THE  PERITONEAL  SYNDROME  IN  MALARIA 

The  definite  localising  signs,  and  the  rapid  rise  in  the  leucocyte 
count  from  8800  to  18,000  in  twelve  hours,  left  no  doubt  in  the 
mind  of  anybody  as  to  the  urgency  of  the  case,  even  though  the 
existence  of  malaria  was  suspected.  In  Cases  II  and  III  the  same 
question  arose  and  the  Medical  Consultant  advised  operation 
until  the  facts  of  Case  I  had  been  related  to  him. 

Causation  of  the  Syndrome.  It  is  evidently  not  from  the  effort  and 
strain  of  vomiting.  Capps  states  that  it  arises  from  coexistent  disease 
or  from  neuralgia  of  malarial  origin,  or  both. 

When  one  considers  the  frequency  of  acute  spleen  tumor  and 
perisplenitis  in  malaria,  and  the  close  relation  of  the  convex  surface 
of  the  spleen  with  the  diaphragm,  I  think  there  is  a  more  rational 
explanation.  Chnically  the  pain  and  tenderness  in  the  left  hypo- 
chondrium  appear  to  be  the  starting  point.  A  tender  spleen  is  almost 
the  rule. 

To  explain  the  symptoms  by  an  extension  of  the  perisplenitis 
to  the  diaphragm  appears  reasonable.  The  abdominal  symptoms  that 
arise  in  the  course  of  diaphragmatic  pleurisy  present  a  striking  paral- 
lel. We  have  all  seen  such  cases  diagnosed  as  acute  abdominal  con- 
ditions, and  some  of  them  operated  upon. 

In  diaphragmatic  pleurisy  and  empyema — the  diaphragm  is 
extensively  involved  in  the  inflammatory  change;  this  has  been 
proved  post-mortem.  Whether  it  be  the  lesion  of  the  diaphragm  itself 
that  gives  rise  to  the  syndrome  directly,  or  indirectly  through  some 
nervous  connexion  or  reflex,  the  mechanism  of  which  we  do  not  as 
yet  understand,  cannot  be  said,  but  the  involvement  of  the  dia- 
phragm appears  to  be  the  origin  of  the  trouble.  The  claim  that  these 
changes  are  of  an  inflammatory  nature  is  supported  by  the  ap- 
pearance of  a  leucocytosis.  In  the  milder  cases  this  is  not  so  appar- 
ent, but  in  the  more  severe  forms,  such  as  those  under  consideration, 
there  is  a  change  sufficiently  great  to  express  itself  by  changes  in 
the  blood. 

BIBLIOGRAPHY 

1.  Semaine  med.,  Paris,  1905,  XXV,  433-5. 

2.  Boston  M.  tf  S.  J.y  1902,  CXLVI,  642-3. 

3.  J.  Am.  M.  Ass.,  Chicago,  1900,  XXXV,  287. 


STUDIES  ON  THE  POTENCY  OF  DIGITALIS  LEAVES 
FROM  VARIOUS  SOURCES 

WITH   COMPARATIVE  TESTS  OF  THE  ACTIVITY  OF  THE  ALCOHOL- 
SOLUBLE   AND   THE   WATER-SOLUBLE    GLUCOSIDES 

By  Joseph  H.  Pratt,  M.D.,  Boston,  Mass. 

STUDIES  on  the  activity  of  digitalis  were  begun  in  the  labora- 
tory of  the  Department  of  Medicine  of  the  Harvard  Medical 
School  in  1909,  and  have  been  continued  to  the  present  time 
by  my  associates  and  myself.  I  was  led  to  undertake  this  work  by 
the  failure  to  obtain  either  therapeutical  or  physiological  effects 
from  digitalis  obtained  from  the  local  druggists  and  at  the  Massa- 
chusetts General  Hospital  when  employed  in  the  ordinary  dosage. 
Even  in  auricular  fibrillation  I  never  produced  the  characteristic 
slowing  of  the  pulse  until  I  used  a  digitalis  leaf  put  up  by  Merck  and 
imported  from  Germany  by  a  pharmacist,  at  my  request. 

On  December  i,  1905,  I  gave  this  powdered  leaf  as  soon  as  it  was 
received  to  a  middle-aged  woman  who  had  cardio-sclerosis,  auricular 
fibrillation,  and  marked  cardiac  insufficiency.  She  had  been  under  my 
observation  for  more  than  a  year.  The  chief  symptoms  were  dyspnea,  a 
troublesome  cough,  edema,  and  a  scanty  output  of  urine.  A  tenth  of  a 
gram  of  the  powdered  leaf  was  given  three  times  a  day.  On  December  8, 
a  week  later,  I  saw  her  again  and  made  the  following  note:  "The  new 
digitalis  has  helped  her  greatly.  The  cough  is  much  less,  the  pulse  is  slow 
but  irregular  and  varies  from  16  to  20  to  the  quarter.  The  rate  at  the 
apex  is  the  same  as  at  the  wrist.  To-day  is  the  first  time  in  six  months  I 
have  found  the  pulse  below  120." 

As  clinical  tests  made  from  time  to  time  strengthened  my  belief 
that  nearly  all  of  the  digitalis  on  sale  in  Boston  was  of  poor  quality, 
I  tested  in  1909  eight  specimens  of  digitalis  leaf  by  the  thirty-minute 
frog  method  as  recommended  by  Gottlieb  (i)  and  Fraenkel.  (2)  A  10 
per  cent  infusion  was  prepared  and  the  minimum  amount  of  digitalis 
required  to  produce  systolic  standstill  of  the  heart  determined. 

^^55 


ii$6  POTENCY  OF  DIGITALIS  LEAVES 

The  species  of  frog  used  in  this  and  later  work  was  Rana  pipiens. 
The  results  are  given  in  the  following  table: 

TABLE  I 

10  Per  Cent  Infusion.  Thirty-minute  Method.  Tests  Madb 
December,  1909 

Mils  of  Digitalis  Infusion  f>er  Gram  of  Frog  Weight  Required  to  Produce 
Systolic  Standstill  of  Heart 

Caesar  &  Loretz,  Halle,  Germany,   "titrated  leaf  V=5" 014 

Merck's  German  leaf 020 

Parke,  Davis  &  Co. — German  leaf 035 

Allen's  English  leaf.     Sample  A 040 

Squibb's  German  leaf. 040 

Allen's  English  leaf.     Sample  B .050 

Allen's  English  leaf.     Sample  C 050 

Shakers  of  Ayer,  Massachusetts  leaf 050 

Squibb's  German  leaf.     Sample  B 050 

The  strongest  leaf  was  one  I  had  obtained  directly  from  Ger- 
many to  compare  with  the  digitalis  sold  in  this  country.  The  second 
in  strength  was  obtainable  only  from  the  druggist  who  imported  it. 
The  biological  analyses  of  the  other  specimens  show  that  they  were 
all  of  poor  quality,  in  fact  four  were  so  weak  in  active  principles 
that  the  characteristic  digitalis  action  on  the  heart  was  not  obtained 
even  when  large  amounts  were  given.  (3) 

A  year  later  Wesselhoeft  and  I  tested  seven  lots  of  digitalis  leaf. 
Instead  of  the  thirty-minute  method  we  employed  a  time  limit  of 
one  hour,  as  originally  suggested  by  Cushny,  and  first  used  by 
Famulener  and  Lyons  (4)  and  later  by  Edmunds  and  Hale  (5)  in  their 
important  studies.  A  10  per  cent  infusion  was  used  in  our  tests, 
while  Edmunds  and  Hale  and  other  American  investigators  em- 
ployed a  tincture.  The  Csesar  &  Loretz  titrated  leaf  V  =  5,  and  the 
Parke,  Davis  &  Co.  leaf  had  been  tested  the  previous  year  by  the 

thirty-minute  method. 

TABLE  II 

10  Per  Cent  Infusion  of  Digitalis  Used.     One-hour  Frog  Method. 
Tests  Made  December,  1910 

Mils  of  Digitalis  Infusion  per  Gram  of  Frog  Weight  Required  to  Produce 
Systolic  Standstill  of  Heart 

Merck's  German  leaf.     Sample  A 007 

Caesar  &  Loretz  titrated  leaf  V  =  5 009 

E.  R.  Squibb  &  Sons.     German  leaf.      Sample  C 012 

Parke,  Davis  &  Co.     German  leaf. 017 

E.  R.  Squibb  &  Sons.     German  leaf.     Sample  D 022 

Merck's  German  leaf.     Sample  B 024 

Allen's  English  leaf.     Sample  D 027 


POTENCY  OF  DIGITALIS  LEAVES  1157 

This  study  brought  out  several  interesting  points.  The  strongest 
leaf  was  obtained  from  the  Boston  druggist,  who  had  kept  a  supply 
of  Merck's  imported  powdered  leaf  in  stock  since  1905.  It  had 
apparently  yielded  good  results  in  the  practice  of  many  physicians 
and  was  held  in  high  repute.  It  was,  however,  not  of  uniform 
strength,  and  one  lot  tested  by  Wesselhoeft  was  found  to  be  weak. 
A  sample  of  the  German  leaf  imported  and  sold  by  Squibb  obtained 
directly  from  this  pharmaceutical  firm  was  of  good  quality.  A 
second  specimen  of  digitalis  put  up  by  Squibb  and  purchased  from 
a  Boston  pharmacist  was  much  weaker.  (Table  II.) 

In  1909  five  different  lots  of  Allen's  English  leaf  had  been 
tested  and  found  to  be  weak.  A  sixth  sample  was  obtained  in  De- 
cember, 191 0.  The  frog  test  showed  it  to  be  less  active  than  the 
other  specimens  of  digitalis  tested  at  that  time,  as  is  shown  in 
Table  II.  It  had  been  assayed  in  England  in  December,  1909,  and 
the  lethal  dose  was  then  .00054  mg.  per  gram  of  frog  weight,  ac- 
cording to  the  statement  on  the  container.  Doubtless  the  alcoholic 
extract  (tincture)  had  been  used  in  the  tests  made  in  England,  and 
the  result  showed  a  high  toxicity  of  the  leaf  at  that  time.  Be  this  as 
it  may,  the  fact  was  established  that  the  aqueous  extract  (infusion) 
prepared  from  six  different  lots  of  Allen's  leaf  contained  a  relatively 
small  amount  of  the  active  principles  of  digitahs.  At  that  time 
Allen's  leaves  had  a  high  reputation  in  America.  The  infusion  from 
these  leaves  was  regarded  as  especially  active.  Hale,  writing  in 
191 1,  said,  "At  the  present  time  Enghsh  leaves  are  considered  to 
be  the  best."  Theodore  Janeway(6),  in  his  excellent  paper  on  "The 
Use  and  Abuse  of  Digitalis,"  published  in  1908,  recommended 
Allen's  leaves  and  favored  the  use  of  the  infusion.  Either  the  stock 
of  Allen's  leaf  that  he  used  was  much  stronger  than  our  specimens, 
or  the  digitalis  generally  dispensed  in  New  York  was  of  very  poor 
quality. 

Although  our  tables  show  that  the  most  active  digitalis  leaves 
assayed  were  obtained  from  Germany  and  that  none  of  the  English 
leaves  were  of  high  activity,  the  conclusion  cannot  be  drawn  that 
the  German-grown  digitalis  is  better  than  English-grown  digitalis. 
It  should  be  noted  that  only  three  lots  of  German  leaf  were  of  high 
value;  two  of  these  were  specially  imp>orted  and  the  third  received 
directly  from  E.  R.  Squibb  &  Sons.  Four  specimens  of  digitalis 


1 158  POTENCY  OF  DIGITALIS  LEAVES 

from  Germany  yielded  an  aqueous  extract  (infusion)  of  low  toxicity, 
and  the  remaining  lot  tested,  which  was  of  a  fair  strength,  was  put 
out  by  Parke,  Davis  &  Co.  for  experimental  study  and  was  not 
purchased  in  the  open  market. 

As  Merck  and  Caesar  &  Loretz  furnished  digitalis  leaves  of 
higher  activity  to  American  pharmacists  than  did  the  English  house 
of  Allen,  it  is  not  surprising  that,  in  this  section  of  the  country  at 
least,  the  German  leaf  in  the  five  years  before  the  war  came  to  be 
held  in  higher  favor  than  the  English,  and  its  use  rapidly  extended. 

Edmunds  (7)  in  1907  examined  three  tinctures  made  from  German 
leaves  and  three  from  English  leaves.  The  German  leaves  gave 
values  of  .004,  .009,  and  .0125  mil;  the  English  values  of  .0055, 
.010,  and  .0145  mil  per  gram  of  frog  weight.  As  the  standard  fixed 
later  by  the  American  Pharmacopoeia  was  a  minimum  dose  of  .006 
mil  of  tincture  per  gram  frog  weight  required  to  produce  systolic 
standstill,  it  is  evident  that  only  one  lot  of  German  and  one  of 
English  leaves  examined  by  Edmunds  yielded  tinctures  of  standard 
strength. 

The  results  obtained  by  Edmunds  is  a  further  indication  of  the 
poor  quality  of  digitalis  used  in  America  at  the  time  our  studies 
were  begun.  In  1908  the  strongest  tincture  tested  by  Edmunds  and 
Hale  was  only  half  the  strength  set  by  the  Pharmacopoeia,  as  .012 
mil  of  this  tincture  per  gram  frog  weight  was  the  dose  necessary  to 
produce  systolic  standstill  of  the  ventricle.  Fluid  extracts  of  digitalis 
from  four  different  manufacturers  (Hance  Bros.  &  White;  Parke, 
Davis  &  Co. ;  Nelson,  Baker  &  Co. ;  and  Sharp  &  Dohme)  diluted 
to  tincture  strength,  were  less  than  one-third  of  the  standard  now 
adopted  by  the  Pharmacopoeia.  The  inexcusable  practice  of  prepar- 
ing so-called  tinctures  of  digitalis  from  fluid  extracts  by  diluting 
with  alcohol  was  fostered  by  one  at  least  of  the  largest  pharmaceu- 
tical firms,  and  I  found  tinctures  were  thus  prepared  by  the  pharma- 
cists of  two  of  the  best  known  American  hospitals,  and  in  general 
use  in  these  institutions. 

Although  Hale  found  that  a  lot  of  Allen's  English  leaves  yielded 
high  assay  values  compared  with  his  assays  of  tinctures  from  leaves 
of  unknown  origin,  even  the  English  leaves  were  not  up  to  the  pres- 
ent standard.  He  did  not  study  the  strength  of  the  watery  extract, 
which  possibly  was  no  stronger  than  in  the  specimens  of  Allen's 


POTENCY  OF  DIGITALIS  LEAVES  1159 

leaves  studied  in  our  laboratory.  Tinctures  made  from  two  lots 
assayed  by  us  yielded  high  values  when  previously  tested  in  England. 

Roth  (8)  examined  in  19 14  twelve  fat-free  tinctures  of  digitalis 
purchased  in  the  open  market  that  year.  They  were  prepared  by 
twelve  of  the  largest  pharmaceutical  firms  in  the  United  States. 
Only  two  of  the  twelve  tinctures  equaled  the  standard  fixed  by 
the  Pharmacopoeia.  On  the  containers  of  six  of  the  samples  the 
statement  was  printed  that  they  had  been  physiologically  assayed. 
All  were  more  active,  however,  than  the  tinctures  tested  by 
Edmunds  and  Hale  in  1908. 

The  titrated  powdered  leaf  prepared  by  Caesar  &  Loretz  was 
supposed  to  be  of  uniform  strength.  It  was  standardized  according 
to  the  method  of  Focke.  (9)  The  claim  was  made  that  it  would 
not  lose  strength.  This  was  doubtless  based  on  the  adoption  of 
Focke's  procedure  of  rapid  drying  of  the  leaf  at  a  temperature  of 
80°  as  soon  as  gathered.  Focke  maintained  that  if  the  leaves  thus 
dried  were  stored  in  air-tight  bottles,  the  loss  in  activity  from  year 
to  year  would  be  negligible.  At  first  they  put  out  a  leaf  with  the  value 
of  5  according  to  Focke's  Formula:  V=j^<.  In  this  formula  Vrepn 
resents  the  potency  of  the  preparation,  which  was  determined  by 
dividing  the  weight  of  the  frog  p  by  the  amount  of  the  10  per 
cent  infusion  d^  multiplied  by  the  time  t  required  for  systolic  stand- 
still to  occur.  A  time  limit  of  not  less  than  seven  or  more  than 
twenty-five  minutes  was  fixed.  In  1903,  when  he  published  his 
method,  he  stated  that  a  good  leaf  should  have  a  value  of  5.  In  1908 
Caesar  &  Loretz  reduced  the  strength  of  the  standardized  leaf  to  4. 

TABLE  III 

Standardized  Leaf  of   Qcsar  &   Loretz  Tested  by  One-hour  Frog  Method. 

10  Per  Cent  Infusion 


Year  of  Crop 

Tested 

Mils  of  Infusion  per 
Gram  Frog  Weight 

1907  (or 

earlier)  V-5. 

E)ecember,    1909             | 

•008 

1910 

V-4. 

November,   1915             | 

•025 

1912 

V-4. 

March,          1917             j 

•023 

1914 

V=4. 

November,   1915             | 

•020 

1915 

November,   1916             | 

•045 

*  Corrected  value,  .02^  mil.    Progs  lued  in  test  resistant  to  digitalis.    The  dose  of  ouabain  required 
to  produce  systolic  standstill  was  twice  the  standard  amount. 

Five  samples  of  Caesar  &  Loretz*  titrated  leaves  have  been  tested 
with  the  results  given  in  Table  III.  All  were  kept  in  the  original 


ii6o  POTENCY  OF  DIGITALIS  LEAVES 

bottles  tightly  corked.  Only  the  first  lot  was  of  high  potency. 
There  was  a  great  difference  between  the  activity  of  this  leaf  and 
the  other  lots,  as  it  was  more  than  twice  the  strength  of  any  of  these. 
The  remaining  four  lots  were  all  practically  of  the  same  potency. 

It  is  thus  seen  that  the  German  leaf  that  was  supposed  to  be 
of  the  highest  quality  and  prepared  in  a  way  to  preserve  its  strength 
unimpaired  was  of  rather  low  activity,  at  least  so  far  as  the  water- 
soluble  alkaloids  were  concerned,  at  the  time  our  tests  were  made. 

American  Digitalis.  Before  the  War  the  greater  part  of  the 
supply  of  digitalis  used  in  the  United  States  came  from  Germany 
and  Austria.  The  pharmocopceial  variety  of  the  plant,  probably 
indigenous  to  central  and  southern  Europe,  escaped  from  cultiva- 
tion and  was  growing  wild  in  great  abundance  in  California,  Oregon, 
and  Washington,  and  to  some  extent  in  West  Virginia  (lo)  (ii), 
but  this  source  of  supply  had  been  neglected. 

In  December,  19  lo,  Wesselhoeft  tested  in  our  laboratory  a 
tincture  made  from  Rocky  Mountain  digitalis  by  E.  R.  Squibb  & 
Sons  nearly  two  years  before  (January,  1909)  and  found  it  to  have  a 
lethal  dose  of  .008  mil  per  gram  frog  weight,  while  the  tincture 
obtained  at  that  time  from  the  Massachusetts  General  Hospital 
made  from  imported  leaves  was  less  than  one-half  that  strength 
when  tested  on  the  same  lot  of  frogs.  In  191 1  Hale  (12)  published 
some  assays  of  American  digitalis  leaves.  He  found  that  a  lot 
grown  in  the  Government  drug  garden  at  Arlington,  Va.,  in  1907, 
and  a  second  lot  of  the  crop  of  19 10,  as  well  as  a  lot  gathered  in 
Madison,  Wis.,  in  1908,  were  all  more  active  than  selected  English 
leaves,  tested  at  the  same  time  for  comparison.  The  lethal  dose 
of  tincture  per  gram  of  frog  weight  for  the  Arlington  leaf  was  .005 
mil,  for  Wisconsin  leaf  .0055  mil,  while  for  the  English  leaf  it  was 
.007  mil.  He  later  tested  garden-grown  first-year  leaves  from  Seattle, 
Wash.,  which  assayed  .006  mil,  and  second-year  wild-growing  leaves 
from  the  same  source  .0085  mil.  As  the  standard  established  by 
the  U.  S.  Pharmacopoeia  IX  is  0.006  mil  of  the  tincture  of  digitalis 
per  gram  of  frog  weight,  it  will  be  seen  that  all  these  American 
leaves  except  the  second-year  Washington  leaf  met  or  exceeded 
this  required  strength,  but  that  the  English  leaf  did  not  quite  meet  it. 

Rowntree  and  Macht  (13),  using  the  cat  method  of  Hatcher  and 
Brody,  found  that  digitalis  from  the  drug  garden  of  the  University 


POTENCY  OF  DIGITALIS  LEAVES 


1161 


of  Wisconsin  was  more  active  than  any  of  four  lots  of  Allen's 
English  leaves  in  use  at  that  time  at  the  Johns  Hopkins  Hospital 
and  far  stronger  than  an  old  stock  of  German  leaf  in  the  hospital 
pharmacy. 

Roth  (11)  in  19 1 7  published  assays  on  eight  lots  of  American 
digitalis.  Four  samples  of  wild  leaf  grown  in  Oregon  were  stronger 
than  the  pharmacopoeial  standard,  as  was  cultivated  Wisconsin 
digitalis  of  the  harvest  of  1916.  One  lot  grown  in  Ohio  (cultivated 
leaf)  equaled  the  standard. 

Morrison  and  I  tested  freshly  prepared  tinctures  made  from 
twenty-three  lots  of  Digitalis  purpurea  grown  in  various  parts  of 
the  United  States  during  the  past  three  years.  The  results  are  given 
in  the  following  table: 

TABLE  IV 

Activity  of  Digitalis  Purpurea  Grown  in  the  United  States.  One-Hour  Frog  Method. 
10  Per  Cent  Tincture  Used  for  the  Tests,  which  Were  Made  at  a  Temperature  of 
20°    C 


Year  of 
Harvest 

Source  of  Leaf 

Mils  of  Tincture  per 
Gram  of  Frog  Weight 

1916     1     Hobart,  Wash.     Wild.     First  year                              | 

003 

1916 

Balleston,  Va.     Cultivated.                                           | 

003 

1916 

University  of  Wisconsin .     Cultivated.                        | 

004 

1915 

University  of  Minnesota.                                               | 

005 

1916 

University  of  Nebraska.     Cultivated.                           | 

005 

1916 

Greenfield,  Ind.     Cultivated.                                        1 

•006 

Washington,  D.  C.     Cultivated.                                   | 

006 

1916 

Portland,  Me.                                                                   | 

007 

1916 

University  of  Minnesota.                                               | 

007 

1917 

Balleston,  Va.                                                                   | 

007 

1915 

University  of  Nebraska.     First  year.                          | 

007 

1917 

Linton,  Ore.                                                                      | 

007 

1916 

Hobart,  Wash.     Wild.     Second  year.                         | 

008 

1916 

Glenolden,  Pa.                                                                  I 

008 

1916 

University  of  Nebraska.                                                 I 

008 

1917 

Linton,  Ore.                                                             '         | 

010 

1917 

Washington.                                                                     | 

Oil 

1918 

Oregon.                                                                              I 

Oil 

1916 

Andover,  Mass.                                                               1 

Oil 

1917 

Linton,  Ore.                                                                      I 

014 

1916     1     Washington.                                                                     I 

014 

1916     1     Seattle,  Wash.     Sample  A.                                            | 

014 

1916     1     Seattle,  Wash.     Sample  B.                                            I 

016 

Only  seven  of  the  twenty-three  lots  of  digitaHs  leaves,  that  is, 
30  per  cent,  yielded  tinctures  which  equaled  or  exceeded  the  stand- 


ii62  POTENCY  OF  DIGITALIS  LEAVES 

ard  of  the  Pharmacopoeia.  The  most  active  leaves  came  from  the 
State  of  Washington  and  from  Virginia,  but  it  should  be  noted  in 
this  connection  that  the  weakest  three  samples  also  came  from 
Washington.  There  were  five  specimens  of  Oregon  leaves,  all  of 
which  were  below  the  standard.  As  Roth  assayed  four  lots  of  wild 
Oregon  leaves  and  all  were  stronger  than  the  Pharmacopoeia 
required,  it  has  been  too  generally  assumed  during  the  past  two 
years  that  any  Oregon  wild  leaf  would  be  suitable  for  use  in 
medicine.  Large  quantities  have  been  gathered  without  prelim- 
inary assay  and  shipped  to  the  eastern  drug  markets.  One  of  our 
two  most  active  samples  was  from  first-year  plants  growing  wild 
in  Washington,  the  other  was  from  cultivated  plants  growing  in 
Virginia. 

Some  of  the  samples  were  air-dried.  Digitalis  received  from  the 
drug  farms  of  the  University  of  Wisconsin  and  the  University  of 
Minnesota  were  in  air-tight  containers.  The  digitalis  from  the 
University  of  Minnesota  was  prepared  according  to  Newcomb*s 
method,  the  leaf  being  dried  in  ovens  at  a  temperature  of  ioo° 
C.  for  eight-hour  periods  on  three  successive  days. 

Our  study  shows  that  highly  active  digitalis  is  grown  in  various 
parts  of  the  United  States,  but  a  large  proportion  of  the  carefully 
collected  samples  of  digitalis  leaves,  70  per  cent,  was  not  as  active 
as  the  Pharmacopoeia  demands.  Probably  the  reason  most  of  the 
digitalis  on  the  market  is  of  low  activity  is  because  a  large  proportion 
of  digitalis  is  of  poor  quality  when  received  by  pharmaceutical  firms. 
In  the  summer  of  191 8  we  examined  a  well-mixed  sample  of  a  large 
lot  of  Oregon  digitalis  amounting  to  830  pounds.  Its  activity  was  a 
httle  more  than  half  the  strength  required  by  the  Pharmacopoeia. 
It  is  evident  from  these  observations  that  samples  should  be  assayed 
before  the  leaf  is  gathered  in  large  quantity. 

Preparation  of  Digitalis.  It  is  held  by  most  investigators  of  the 
subject  that  the  leaves  should  be  quickly  dried  by  artificial  heat 
as  soon  as  gathered.  Enzymes  that  break  down  the  glucosides  are 
rendered  inactive  by  a  high  temperature.  According  to  Focke  (9) 
the  leaves  should  be  dried  at  a  temperature  not  exceeding  80° 
within  three  days  of  gathering  until  the  moisture  content  is  reduced 
to  1.5  per  cent.  Hale  (12)  found  that  heat  up  to  120°  could  be  applied 
for  at  least  two  hours  to  partially  dried  leaves,  containing  10  per 


POTENCY  OF  DIGITALIS  LEAVES  1163 

cent  moisture,  without  causing  a  loss  of  activity.  Newcomb  (10) 
believes  that  leaves  should  be  dried  at  a  temperature  of  100°  for 
eight  hours  on  three  successive  days.  This  reduces  the  moisture  to 
about  4  per  cent.  Roth  (11)  found  that  three  specimens  of  Oregon 
leaf  that  had  been  dried  in  the  air  were  of  unusual  strength.  The 
most  active  sample  assayed  by  him  consisted  of  leaves  that  had 
partially  dried  on  the  stalk. 

Whether  the  low  activity  of  the  Oregon  leaves  we  have  examined 
was  due  to  lack  of  glucosides  in  the  leaves,  or  to  improper  drying, 
cannot  be  stated.  Although  the  method  of  drying  is  doubtless  of 
importance,  variation  in  the  toxicity  of  new  digitalis  probably 
depends  more  on  the  amount  of  active  glucosides  contained  in  the 
fresh  leaves.  Digitalis  obtained  from  the  drug  farm  of  the  University 
of  Minnesota  was  carefully  dried  under  Professor  Newcomb's 
supervision  and  was  shipped  in  an  air-tight  container.  The  toxicity 
of  the  tincture  was  less  than  that  of  some  samples  that  were  not 
prepared  with  such  care.  The  watery  extract  of  the  Minnesota  leaf 
was  strong,  the  minimum  lethal  dose  being  .007  mil.  It  is  quite 
probable  that  rapid  drying  at  a  temperature  of  lOO**  C.  preserves 
the  active  principles  that  are  soluble  in  water  better  than  methods 
in  which  less  heat  is  employed. 

Relation  of  Moisture  Content  to  Deterioration.  It  is  generally 
held  that  the  more  moisture  left  in  the  leaves  the  more  rapid  the 
deterioration.  Focke  holds  that  the  moisture  content  should  be 
reduced  to  1.5  per  cent  within  three  days  after  gathering.  The  leaf 
is  hydroscopic,  but  if  moisture  is  taken  up  later,  he  claims  little 
loss  of  strength  may  result.  All  samples  of  digitaHs  tested  by 
Wesselhoeft  and  myself  contained  much  more  than  1.5  per  cent 
of  moisture. 

A  study  of  Table  V  shows  there  was  no  relation  between  the 
percentage  of  moisture  and  the  activity  of  leaf  as  tested  on  frogs 
with  a  10  per  cent  aqueous  extract.  Hale,  using  tinctures,  was  like- 
wise unable  to  find  any  parallelism  between  moisture  content  of 
the  leaves  and  the  toxic  value.  Undoubtedly  some  of  the  moisture 
present  had  been  absorbed  by  the  leaves  after  drying.  If  the  Caesar 
&  Loretz  leaves  had  been  dried  according  to  Focke's  instructions 
and  preserved  without  the  addition  of  moisture  they  would  have 
contained  only  1.5  per  cent.  It  should  be  noted  that  the  leaves  from 


1 164 


POTENCY  OF  DIGITALIS  LEAVES 


the  University  of  Minnesota  dried  at  100°  contained  more  moisture 
than  some  of  the  other  samples. 

TABLE  V 

Percentage  of  Moisture  in  Sample  of  Digitalis  and  Minimum  Lethal  Dose 
PER  Grams  of  Frog  Weight 


Per  Cent 
Moisture 

Mils  of  10  Per  Cent 

Infusion  per 
Gram  Frog  Weight 

Caesar  &  Loretz.     Folia  digitalis  titrata  V  =  5. 

5-5 

•008 

Caesar  &  Loretz.     Folia  digitalis  titrata  1910,  V=«4. 
Newly  opened  bottle. 

59 

•  015 

Merck's  powdered  leaves.     Old  stock. 

61 

•024 

E.  R.  Squibb  &  Sons'  powdered  leaves.     Newly  opened 
can. 

6-3 

•  012 

University  of  Minnesota.     Newly  opened  can. 

6-3 

•007 

Parke,  Davis  &  Co.     Powdered  leaf. 

7-6 

■017 

Hobart,  Wash. 

7-6 

•008 

Allen's  English  leaves.     Old  Stock.                                   ]       7-8 

•027 

Glenolden,  Pa.                                                                       |       8-7 

•Oil 

Merck's  powdered  leaf.     Newly  opened  bottle.               |       91 

•007 

Deterioration  oj  Digitalis  Preparations.  Comparative  tests  have 
been  made  over  a  series  of  eight  years.  Specimens  of  dried  leaves 
retained  their  strength  well.  There  was  very  little  deterioration 
either  of  the  alcohoI-soIuble  or  the  water-soluble  glucosides.  It  has 
been  shown  by  a  number  of  investigators  that  tinctures,  as  a  rule, 
do  not  keep  well.  Symes,  (14)  in  a  careful  study,  found  that  deteriora- 
tion may  begin  within  a  month  from  the  time  of  manufacture,  but 
one  tincture  examined  by  him  and  reputed  to  be  twelve  years 
old  had  an  activity  in  excess  of  the  standard.  We  tested  two 
tinctures  over  a  period  of  eight  years;  one,  a  tincture  made  from 
Rocky  Mountain  digitalis,  which  had  a  minimum  lethal  dose  of 
.008  mil  in  1910,  required  .021  mil  in  19 17.  A  tincture  from  the 
Caesar  &  Loretz  leaf,  V  =  5,  had  an  activity  of  .006  mil  per  gram 
when  freshly  prepared  in  January,  19 10;  in  April,  191 7,  the  lethal 
dose  of  this  tincture  was  .021  mil.  It  is  thus  seen  that  more  than 
three  times  the  dose  was  required  in  1917  than  in  19 10  to  produce 
the  same  effect. 

Comparative  Tests  of  the  Alcohol-soluble  and  the  Water-soluble 
Glucosides.  In  a  large  number  of  specimens  of  digitalis  obtained  from 
various  sources  Morrison  and  I  studied  the  relative  toxicity  of  a 
10  per  cent  alcoholic  extract  (tincture)  and  a  10  per  cent  infusion. 


POTENCY  OF  DIGITALIS  LEAVES  ii6$ 

For  years  the  infusion  of  digitalis  has  been  held  in  high  esteem  by 
many  clinicians,  and  it  is  possible  that  the  water-soluble  principles 
of  the  leaf  are  more  important  in  therapeutics  than  those  that  add 
toxicity  to  the  tincture  but  are  not  extracted  by  water. 

Different  lots  of  digitalis  leaves  vary  widely  in  the  relative 
amount  of  alcohoI-soIuble  and  water-soluble  principles  they  con- 
tain as  estimated  by  the  biological  test.  Comparative  tests  of  the 
toxic  power  of  both  the  alcoholic  extract  and  the  aqueous  extract 
were  made  on  twenty-one  different  lots  of  digitalis  leaves.  The 
strongest  lo  per  cent  alcohoHc  extract  (tincture)  had  a  value  of 
.003  mil  per  gram  of  frog  weight,  the  strongest  aqueous  extract 
.007  mil.  The  weakest  alcoholic  extract  .016  mil,  the  weakest  aqueous 
extract  failed  to  produce  systolic  standstill  of  the  heart  when  .045 
mil  per  gram  were  given.  Three  samples  of  leaves  yielded  an  extract 
with  an  activity  of  .008  mil.  The  alcoholic  extracts  from  these  three 
samples  had  values  of  .003,  .005,  and  .006  mil.  Leaves  then  of  equal 
strength  in  water-soluble  principles  may  vary  100  p>er  cent  in 
the  activity  of  the  alcohoI-soIuble  principles. 

The  alcoholic  extract  was  always  found  somewhat  stronger  than 
the  aqueous  extract,  although  the  difference  was  slight  in  some 
specimens.  The  carefully  dried  leaf  from  the  University  of  Minne- 
sota gave  values  of  .005  mil  for  the  alcohoHc  extract  and  .007  mil 
for  the  aqueous  extract.  The  Caesar  &  Loretz  titrated  leaf  V  =  S» 
which  contained  less  moisture  than  any  other  specimen,  and  had 
been  dried  rapidly  if  Focke's  directions  had  been  followed,  was 
found  to  have  an  activity  of  .006  mil  for  the  alcoholic  extract  and 
.008  mil  for  the  aqueous  extract.  Leaf  from  plants  grown  in 
Indiana  from  Oregon  seed  and  from  the  Bureau  of  Plant  Industry, 
Washington,  D.  C,  Hkewise  yielded  values  of  .006  mil  for  the 
tincture  and  .008  mil  for  the  10  per  cent  infusion.  From  no  other 
lots  of  digitalis  leaves  were  alcoholic  and  aqueous  extracts  obtained 
that  were  so  nearly  of  the  same  strength.  As  the  University  of 
Minnesota  leaf  and  the  Caesar  &  Loretz  digitalis  were  the  two 
lots  of  leaves  that  were  known  to  be  dried  at  a  high  temperature 
soon  after  gathering,  our  results  suggest  that  the  aqueous-soluble 
glucosides  were  better  preserved  by  the  special  methods  of  drying 
than  by  the  methods  of  slow  drying  at  lower  temperatures  which 
are  in  general  use.  We  do  not  know  how  the  Indiana  leaves  or  those 


ii66  POTENCY  OF  DIGITALIS  LEAVES 

furnished  by  the  Bureau  of  Plant  Industry  were  prepared,  and  the 
fact  that  the  most  rapidly  dried  leaves  contained  a  large  proportion 
of  water-soluble  glucosides  may  have  been  merely  a  coincidence. 

There  is  evidence,  as  shown  by  Kraft,  (15)  that  the  most  impor- 
tant water-soluble  glucoside  (digitalein  or  gitalin)  is  easily  decom- 
posed. It  had  long  been  held  that  the  active  glucosides  in  the  presence 
of  moisture  change  into  substances  that  are  inert  or  injurious.  Some 
leaves  containing  13  per  cent  of  moisture  were  kept  eight  years  in 
the  laboratory  and  then  alcoholic  and  aqueous  extracts  were  pre- 
pared and  tested.  The  former  had  a  value  of  .009  mil  per  gram  frog 
weight,  while  the  latter  required  .026  mil  per  gram  to  produce  sys- 
tolic standstill. 

Our  study  indicates  that  the  toxicity  of  the  aqueous  extract  is 
probably  a  better  guide  to  the  therapeutic  value  of  a  digitalis  leaf 
than  the  alcoholic  extract.  At  the  present  time  the  alcoholic  extract 
(tincture)  is  used  almost  exclusively  in  the  biological  tests  of  digitalis 
by  the  frog  method  in  America  and  England.  The  value  of  the  aque- 
ous extract  of  leaves  used  for  the  preparation  of  infusions  should 
be  biologically  determined  on  frogs  or  cats,  as  many  lots  of  digitahs 
were  rated  as  fairly  strong  when  the  toxicity  of  the  tincture  was 
taken  as  the  test,  but  which  yielded  infusions  of  low  value. 

The  region  where  the  digitalis  grew  seemed  to  influence  the  ratio 
of  water-soluble  to  alcohoI-soIuble  glucosides.  Three  specimens  of 
digitalis  cultivated  in  New  England  were  all  weak  in  the  water- 
soluble  glucosides,  while  tinctures  prepared  from  two  of  them  were 
fairly  strong. 

Digitalis  stronger  in  water-soluble  glucosides  than  the  best  ob- 
tainable titrated  German  leaf — that  of  Caesar  &  Loretz — grows  in 
the  United  States  and  can  now  be  obtained  and  is  available  com- 
mercially. The  water-soluble  principles  were  assayed  by  the  frog 
method,  using  a  10  per  cent  infusion  in  twenty  specimens  of  Ameri- 
can leaf  collected  from  various  sources.  Fourteen  of  these  were 
stronger  in  water-soluble  glucosides  than  any  lot  of  Caesar  &  Loretz 
titrated  leaf  purchased  since  1909.  Selected  and  biologically  tested 
Virginian  leaf  bought  in  the  open  market  in  the  fall  of  191 8  had  a 
value  of  .008  mil  of  10  per  cent  infusion,  while  the  strongest  Caesar 
&  Loretz  leaf  V  =  4  had  a  value  of  .020  mil.  The  tests  showed  that 
the  American  leaf  was  two  and  a  half  times  as  strong  in  water- 


POTENCY  OF  DIGITALIS  LEAVES  1167 

soluble  glucosides  as  the  best  German  digitalis  that  could  be  ob- 
tained before  the  war. 

Summary.  Most  of  the  samples  of  digitalis  imported  from  Eng- 
land and  Germany  before  the  war  were  below  the  standard  now 
required  by  the  American  Pharmacopoeia,  and  were  too  weak  to 
produce  physiological  or  therapeutic  effects  when  given  in  the 
usual  dosage. 

Most  of  the  digitalis  collected  from  different  parts  of  the  United 
States  during  the  past  three  years  likewise  failed  to  yield  tinctures 
that  were  equal  in  strength  to  that  demanded  by  the  Pharmacopoeia. 
Some  of  the  digitalis  grown  in  the  United  States,  both  wild  and 
cultivated,  has  been  found  by  biological  tests  to  be  as  strong  as 
any  imported  digitalis  examined. 

The  alcohoI-soIuble  and  water-soluble  glucosides  vary  in  amount 
in  different  samples  of  digitalis.  As  the  latter  are  probably  more 
important  in  therapeutic  activity,  it  would  seem  that  the  infusion 
should  be  used  in  the  biological  assay. 

BIBLIOGRAPHY 

1.  Gottlieb,  MiXncben.  med.  Wcbnscbr.,  1908,  LV,  1265. 

2.  Fraenkel,  Ergebn.  d.  inn.  Med.  u.  Kinderb.,  1908,  I,  88. 

3.  Pratt,  Boston  M.  €f  S.  J.,  1910,  CLXIII,  279. 

4.  Famulener  and  Lyons,  Proc.  Am.  Pbarm.  Ass.,  1902,  L,  415. 

5.  Edmunds  and  Hale,  Hyg.  Lab.  Bull.  XLVIII,  Wash.,  1909. 

6.  Janeway,  Am.  J.  M.  Sc,  1908,  CXXXV,  781. 

7.  Edmunds,  J.  Am.  M.  Ass.,  1908,  XLVIII,  1744. 

8.  Roth,  Hyg.  Lab.,  Bull.  102,  Wash.,  1916. 

9.  Focke,  Arcb.  d.  Pbarm.,  1903,  CCXLI,  128. 

10.  Newcomb,  Am.  J.  Pbarm.,  1912,  LXXXIV,  201. 

11.  Roth,  Public  Healtb  Reports,   U.  S.  Public  Health   Service,   Wash., 

1917,  377. 

12.  Hale,  Hyg.  Lab.  Bull.  74,  Wash.,  191 1. 

13.  Rowntree  and  Macht,  J.  Am.  M.  Ass.,  1916,  LXVI,  870. 

14.  Symes,  Brit.  M.  J.,  June  20,  1914. 

15.  Kraft,  Arcb.  d.  Pbarm.,  1912,  CCL,  118. 


EPIDEMIC  INFLUENZA  IN  CHILDREN 
By  John  Ruhrah,  M.D.,  Baltimore,  Md. 

THE  epidemic  of  so-called  influenza  which  prevailed  in  Balti- 
more in  the  winter  of  191 8  and  19 19,  and  which  affected 
children  to  a  very  considerable  degree,  presented  a  certain 
clinical  picture  not  ordinarily  met  with  in  practice,  and  therefore 
merits  a  description. 

In  almost  every  instance  in  which  the  disease  occurred  in  a  house- 
hold all  the  children  exposed  contracted  it;  occasionally  one  or  more 
escaped.  In  the  early  part  of  the  epidemic  the  disease  was  usually  intro- 
duced into  a  household  by  one  of  the  older  members  of  the  family,  the 
children  being  affected  generally  within  five  days  after  exposure.  All 
became  ill  on  the  same  day  or  within  a  period  of  two  or  three  days,  so  that 
in  almost  every  dwelling  in  which  the  disease  was  introduced  the  entire 
family  was  in  bed  at  the  same  time.  Later  in  the  epidemic  instances  were 
noted  in  which  the  adults  escap>ed  and  the  disease  started  in  the  chil- 
dren, although  in  some  instances  adults  were  subsequently  affected.  The 
disease  was  apparently  transmitted  by  direct  contact,  but  isolation  in  a 
household  was  rarely  successful  in  preventing  the  spread  to  other  mem- 
bers of  the  family,  nor  did  masks  seem  to  help  in  private  residences. 
Whether  this  was  due  to  the  imperfect  technic  employed,  or  to  infec- 
tions through  the  mucous  membranes  of  the  eye,  is  not  clear. 

The  clinical  picture  was  striking,  usually  quite  definite,  and  not  like 
an  ordinary  cold.  The  child  was  almost  invariably  taken  ill  suddenly; 
sometimes  the  onset  could  be  dated  almost  to  the  minute.  In  these  cases 
the  disease  started  with  a  vomiting  attack  or  a  slight  chill,  followed  by 
high  fever  and  marked  prostration,  but  sometimes  there  were  prodromes 
of  an  indefinite  nature  lasting  for  about  twenty-four  hours  or  less.  The 
prostration  was  usually  marked,  the  child  was  perfectly  willing  to  be 
in  bed,  the  face  was  flushed  with  a  curious  reddish-purple  blush  over  both 
cheeks  and  sometimes  over  the  entire  face  and  neck,  and  this  blush  was 
sometimes  very  cyanotic,  so  as  to  produce  a  decided  purplish  tinge. 

There  was  a  marked  conjunctivitis,  usually,  though  not  always, 
without  much  secretion,  and  occasionally  there  was  noticeable  photo- 

1168 


EPIDEMIC  INFLUENZA  IN  CHILDREN  1169 

phobia.  Sometimes  this  was  wanting,  while  in  other  cases  it  was  so  in- 
tense as  to  suggest  that  seen  in  meningitis.  In  a  few  children  there  was 
inflammation  of  the  ocular  conjunctivse,  which  sometimes  was  limited 
to  one  eye. 

In  some  cases  there  was  a  nasal  discharge  from  the  beginning  of  the 
disease,  while  in  others  this  did  not  start  until  one  to  three  days  after 
the  initial  rise  of  temperature.  In  some  instances  the  discharge  was  ex- 
tremely profuse  and  irritated  the  skin  about  the  nose,  and  in  others  there 
was  comparatively  little.  In  practically  all  there  was  a  marked  angina, 
the  entire  pharynx  and  tonsils  and  soft  palate  being  intensely  red  and 
somewhat  swollen.  This  inflammation  extended  over  the  hard  palate  and 
cheeks,  but  there  was  nothing  which  could  be  called  a  pathognomonic 
enanthem.  Small  punctate  hemorrhages  were  not  uncommon.  This  in- 
flammation generally  spread  downward  rapidly,  in  some  involving  the 
larynx,  with  production  of  hoarseness  and  croupy  cough,  and  occasion- 
ally a  laryngitis  so  severe  as  to  require  intubation.  In  others  there  was  a 
tracheitis  with  considerable  cough;  while  in  most  there  was  a  bronchitis, 
frequently  extending  even  to  the  finer  bronchial  tubes.  This  produced 
slight  acceleration  of  breathing,  and  there  was  usually  a  great  deal  of 
irritable  coughing.  The  amount  of  secretion  varied,  in  some  being  very 
profuse,  in  others  more  or  less  limited.  Occasionally  there  was  a  dry 
bronchitis  with  an  extremely  irritable  cough,  but  apparently  slight  se- 
cretion. 

Children  were  more  or  less  exempt  from  the  pneumonic  complica- 
tions so  common  in  older  people,  but  not  entirely  so.  In  infants  under 
fifteen  months  of  age  broncho-pneumonia  was  not  infrequently  encoun- 
tered, and  presented  no  particular  diff^erence  from  that  ordinarily  seen, 
unless  it  was  that  most  cases  were  of  a  rather  severe  type.  In  older  chil- 
dren there  was  an  occasional  broncho-pneumonia  or  lobar  pneumonia, 
and  sometimes  either  an  empyema  or  a  serous  exudate  into  the  pleural 
cavity. 

Otitis  media  and  involvement  of  the  mastoid  were  both  comparatively 
infrequent,  although  owing  to  the  large  number  of  cases  seen  this  com- 
plication was  encountered  often  enough. 

In  most  children  the  gastro-intestinal  tract  was  not  much  disturbed 
apart  from  an  occasional  attack  of  vomiting,  unless  the  child  was  forced 
to  take  food.  In  practically  every  instance  where  this  was  done  an  irri- 
table condition  of  the  stomach  was  produced  which  lasted  for  several  days, 
during  which  time  little  or  nothing  could  be  retained.  In  a  certain  number 
of  cases  the  other  symptoms  were  mild,  while  there  was  very  marked  in- 
volvement of  the  gastro-intestinal  tract,  often  with  diarrhea  and  a  ten- 


1 170  EPIDEMIC  INFLUENZA  IN  CHILDREN 

dency  to  production  of  an  acidosis.  These  generally  recovered  in  two  or 
three  days  if  the  stomach  was  not  irritated  by  food  or  medication. 

There  was  some  albuminuria  in  cases  with  high  fever,  but  the  writer 
did  not  see  any  cases  of  nephritis  due  to  influenza,  with  possibly  one  ex- 
ception where  the  etiology  was  somewhat  obscure. 

The  nervous  symptoms  were  either  a  marked  irritability,  or,  what 
was  more  common,  a  condition  of  drowsiness  or  stupor,  sometimes 
almost  amounting  to  coma,  although  the  child  could  be  easily  aroused, 
but  generally  objecting  to  the  interference  and  drifting  off  into  slumber 
almost  immediately.  Occasionally  there  were  mild  symptoms  of  meningis- 
mus,  consisting  of  slight  retraction  of  the  head,  very  marked  headache, 
some  dilatation  of  the  pupils,  with  somewhat  lessened  reaction  to  light. 
In  one  child  a  marked  influenza  meningitis  was  observed. 

The  temperature  presented  several  variations,  all  of  which  were 
frequently  met  with.  In  a  large  proportion  of  cases  in  patients  under  fifteen 
years  of  age  the  temperature  was  highest  at  the  onset  and  gradually  became 
lower  and  disappeared  within  three  days.  This  led  to  the  term  "three- 
day  fever."  In  other  cases  the  temperature  reached  normal  on  the  third 
day,  remained  normal  one  or  two  days,  and  then  recurred  for  two  or  three 
more  days,  when  the  normal  point  was  again  reached.  In  either  case  the 
temperature  was  high  for  two  or  three  days,  then  down  in  the  morning 
to  normal  or  below  normal  and  very  high  in  the  evening,  104°  to  105*  or 
more,  gradually  returning  to  normal.  In  one  or  two  instances  this  high 
irregular  temperature  persisted  for  ten  days  or  more  without  any  apparent 
complication.  In  almost  every  case  in  which  the  child  was  allowed  to  be 
up  on  the  day  following  the  fever,  and  particularly  where  any  consider- 
able physical  exercise  was  indulged  in,  there  was  an  immediate  return  of 
temperature  and  other  symptoms  which  lasted  from  two  to  five  or  more 
days.  After  the  second  remission  of  temperature,  when  the  normal  point 
was  again  reached,  any  further  rise  was  taken  to  mean  some  complicating 
inflammation.  In  many  the  high  temperature  was  followed  by  two  or  three 
days  of  subnormal  temperature. 

The  skin  manifestations  are  important  from  the  standpoint  of  diagnosis, 
although  not  pathognomonic.  In  addition  to  the  purplish  blush  on  the  cheeks 
referred  to  above  there  was  generally  a  diffuse  redness  and,  in  the  severer 
cases,  a  diff'use  congestion.  This  varied  from  time  to  time,  but  was  present 
in  almost  all  cases  to  a  greater  or  less  degree.  The  pressure  of  the  stetho- 
scope or  of  the  hands  left  white  areas  which  rather  rapidly  again  became 
congested.  In  addition  to  this  there  were  frequently  small  areas  of  an  urti- 
carial-like  eruption.  There  was  also  in  many  an  eruption  resembling  some- 
what the  rose  spots  seen  in  typhoid  ever  for  the  similar  eruption  seen  in 


EPIDEMIC  INFLUENZA  IN  CHILDREN  1171 

colon  bacillus  infections.  These  varied  in  number  and  were  usually  most 
frequent  on  the  chest,  abdomen,  and  back,  sometimes  on  the  extremities 
and  occasionally  on  the  face.  Once  or  twice  they  were  so  numerous  as 
to  lead  to  a  lay  diagnosis  of  measles. 

Fatalities  were  uncommon,  although  where  nursing  was  poor  the  cases 
with  broncho-pneumonia  very  often  died.  Where  proper  care  was  given 
there  were  few  mishaps  except  among  children  under  two  years  of  age. 
In  addition  to  the  deaths  from  broncho-pneumonia  there  were  some  very 
curious  and  intense  infections.  These  patients  were  profoundly  ill  from  the 
onset,  markedly  cyanosed,  and  more  or  less  unconscious,  with  a  high 
fever.  There  was  much-disturbed  heart  action  and  irregular  respiration, 
sometimes  vomiting,  and  death  supervened  generally  within  forty-eight 
hours  after  the  onset.  These  cases  were  unaffected  by  treatment,  and  the 
heart  generally  did  not  respond  to  stimulation,  or  if  so,  only  for  a  transient 
period. 

The  diagnosis  was  comparatively  easy  in  early  life  on  account  of 
the  rather  clear-cut  symptomatology.  The  prognosis  in  children 
was  good  if  one  excepted  the  broncho-pneumonias,  which  were  rather 
infrequent.  The  treatment  was  symptomatic. 


AN  UNUSUAL  COMPLICATION  OF  MUMPS 
By  Joseph  Sailer,  M.D.,  Philadelphia,  Pa. 

THE  seriousness  of  mumps  as  a  disease  when  it  occurs  in  epi- 
demic form  has  never  been  justly  estimated.  In  large  groups 
the  financial  loss  to  the  employer  of  the  patients'  time  may 
be  considerable.  The  disease  is  not  dangerous  to  life.  Rarely  does 
it  produce  any  sequel  that  impairs  function;  hence  little  attention 
has  been  paid  to  it  from  the  standpoint  of  prophylaxis. 

As  nearly  as  can  be  determined  the  organism  finds  a  culture 
medium  upon  which  it  can  grow  actively  and  produce  its  poisonous 
products,  chiefly  in  the  glandular  tissues,  salivary  glands,  pancreas,  and 
testicles.  Trousseau  particularly  has  described  the  so-called  cerebral 
mumps,  a  rare  complication  characterized  by  acute  delirium  or 
insanity,  lasting  usually  twenty-four  hours.  I  have  seen  one  such 
case  in  Vichy  Hospital  Center  in  France  following  closely  the  de- 
scription given  by  Trousseau.  In  this  instance  a  spinal  puncture  was 
not  done,  and  we  have  no  knowledge  regarding  the  reason  that 
caused  the  cerebral  disturbance.  The  rapid  recovery  from  a  condi- 
tion of  delirium,  during  which  the  man  attempted  to  throw  himself 
from  the  window  of  the  ward,  was  the  surprising  feature. 

During  the  winter  of  191 7-1 8,  while  I  was  in  charge  of  the 
Medical  Wards  of  the  Base  Hospital,  Camp  Wheeler,  there  was  a 
brief  epidemic  of  mumps  among  the  soldiers  in  the  camp  that 
yielded  about  6000  cases,  the  notable  feature  of  which  was  the 
extraordinary  rapidity  of  its  spread.  More  than  half  of  the  cases 
developed  within  a  period  of  two  weeks,  although  there  were  several 
occasions  before  and  afterward  during  which  there  were  minor 
exacerbations. 

Nothing  could  be  learned  about  the  mode  of  transmission.  It 
seemed  as  if  contact  would  hardly  explain  its  extraordinarily  rapid 
spread  through  the  camp,  nor  as  nearly  as  we  could  ascertain  did 
it  seem  to  start  at  one  or  more  foci  and  gradually  extend  from  them. 
Cases  appeared  almost  simultaneously  in  all  parts.   There  was 

1 172 


AN  UNUSUAL  COMPLICATION  OF  MUMPS      1173 

nothing  that  justified  a  suspicion  of  insect  transmission.  In  fact  at 
the  time  of  the  maximum  incidence  the  camp  was  almost  free  of 
any  form  of  biting  insect,  including  fleas,  lice,  and  bedbugs. 
The  features  that  impressed  me  most  particularly  were: 

(i)  The  involvement  of  all  the  salivary  glands.  The  parotid  gland 
was  most  frequently  and  nearly  always  most  conspicuously  involved, 
but  when  sought  the  submaxillary  and  subinguinal  glands  were  so  fre- 
quently found  swollen  and  tender  that  we  concluded  that  mumps  respects 
them  almost  as  little  as  it  does  the  parotids. 

(2)  The  evidence  of  orchitis,  which  is  a  true  metastatic  manifestation, 
efforts  to  prevent  infection  through  the  urethra,  and  the  administration  of 
urotropin  were  equally  ineffectual. 

(3)  The  difficulty  of  proving  conclusively  that  the  abdominal  symptoms 
were  due  to  involvement  of  the  pancreas.  Various  tests  were  employed,  but 
none  was  positive.  These  symptoms  were  exceedingly  frequent. 

(4)  The  occurrence  of  a  complication  not  hitherto  described  that  I 
was  led  to  believe  indicated  an  involvement  of  the  thymus  gland.  Alto- 
gether six  cases  of  this  syndrome  were  observed,  Yxo  of  i  per  cent  of  all 
cases. 

The  general  features  of  all  of  these  cases  were  so  similar  that  in  spite 
of  a  slight  variation  in  severity  they  may  be  described  together.  Usually 
on  the  third  or  fourth  day  of  the  disease,  and  sometimes  later,  swelling 
was  observed  over  the  manubrium  of  the  sternum.  This  swelling  was 
usually  considerable,  not  sharply  circumscribed.  The  tissue  pitted  on  pres- 
sure and  there  was  either  no  discoloration  or  very  slight  erythema,  which 
often  extended  down  the  middle  of  the  sternum  and  on  either  side  as  far  as 
the  midclavicular  line,  obliterating  the  supersternal  notch. 

Physical  examination  at  this  time  showed  dullness  over  the  manubrium. 
The  note  became  distinctly  more  resonant  when  the  head  was  thrown 
back,  the  sign  that  is  supposed  to  indicate  enlargement  of  the  thymic  gland. 
There  was  no  local  tenderness,  distinct  dyspnea,  not  severe  enough  in  any 
case  to  cause  orthopnea,  and  there  was  no  stridulous  breathing  on  auscul- 
tation. 

The  x-ray  was  tried  in  all  cases,  and  it  was  the  opinion  of  Major 
Wheat,  who  took  great  pains  to  obtain  profile  exf>osures,  that  a  shadow 
could  be  seen  back  of  the  manubrium,  indicating  enlargement  of  the 
thymus.  The  thyroid  gland  did  not  share  in  this  enlargement. 

During  the  persistence  of  the  swelling  there  was  a  slight  elevation  of 
temperature,  but  the  symptoms  were  not  otherwise  particularly  severe. 
The  edema  was  usually  observed  in  slight  form  on  the  first  day,  reaching 


1 174      AN  UNUSUAL  COMPLICATION  OF  MUMPS 

its  maximum  the  second  or  third  day,  and  disappearing  on  the  fourth 
or  fifth  day.  As  it  subsided  the  dyspnea  ceased  and  the  patient  returned 
to  a  normal  state  of  health.  There  were  no  sequelae.  The  change  in  note 
over  the  manubrium  as  the  head  was  moved  forward  and  backward  ceased 
and  a  persistent  resonant  note  was  obtained. 

The  evidence  that  the  thymus  was  involved  may  be  regarded  as 
suggestive  but  inadequate.  Favorable  are,  first,  the  location  of  the 
edema;  second,  the  alteration  in  the  percussion  note;  third,  the 
dyspnea,  and  fourth,  the  x-ray  plates. 

Against  this  is  the  absence  of  evidence  that  the  ductless  glands 
are  ever  involved  in  mumps.  It  is,  however,  possible  that  in  the 
cerebral  forms  the  pituitary  gland  is  the  seat  of  the  active  process. 
There  is,  however,  no  direct  evidence  that  this  is  true.  A  very  re- 
stricted access  to  the  literature  failed  to  reveal  any  record  of  such  a 
complication,  but  in  discussing  the  matter  with  others  in  the  Medical 
Corps  of  the  United  States  Army  who  had  observed  large  epidemics 
of  mumps,  two  similar  observations  were  reported.  At  any  rate  it 
can  be  definitely  said  that  in  the  course  of  mumps  there  occurs  a 
presternal  edema  associated  with  slight  dyspnea  and  yielding  physi- 
cal signs  and  x-ray  pictures  that  suggest  enlargement  of  the  thymus, 
that  this  occurs  in  about  one  case  in  a  thousand  of  mumps,  and  is 
probably  not  quite  as  rare  as  the  so-called  cerebral  complication. 


SEGMENTAL  CEREBRAL  MONOPLEGIA 
By  William  G.  Spiller,  M.D., 

Professor  of  Neurology  in  the  University  of  Pennsylvania 

CORTICAL  or  subcortical  monoplegia  in  which  the  paralysis 
is  confined  to  a  very  limited  portion  of  a  limb  is  of  rare 
occurrence,  at  least  in  civil  practice.  It  is  doubtful  whether 
it  could  occur  from  a  lesion  as  low  as  the  inner  capsule.  The  subject 
has  attracted  attention  for  years,  but  the  observations  have  been 
comparatively  few.  A  knowledge  of  this  form  of  paralysis  is 
important,  because  an  incorrect  diagnosis  is  probable  when  the 
patient  is  first  seen,  especially  when  there  has  been  no  injury  of 
the  head.  A  paralysis  when  confined  in  the  upper  limb  to  the 
shoulder  muscles  may  be  associated  with  weakness  or  even  complete 
paralysis  of  the  hip  muscles  or  of  all  of  those  of  the  lower  limb  of 
the  same  side.  When  confined  in  the  upper  limb  to  the  hand  muscles 
it  may  be  associated  with  partial  or  complete  paralysis  of  the 
face  of  the  cerebral  type  and  with  paralysis  of  the  tongue,  on  the 
same  side  as  the  hand  paralysis.  The  explanation  of  this  association 
is  to  be  found  in  the  propinquity  of  the  hip  center  to  the  shoulder 
center,  and  of  the  hand  center  to  the  face  center.  A  cortical  jmr- 
alysis  confined  to  the  hand  is  very  suggestive  of  f>eripheral  nerve 
lesion,  but  impairment  of  stereognosis  and  of  the  senses  of  position 
and  passive  movement  with  preservation  of  other  forms  of  sensa- 
tion suggests  the  cerebral  origin,  and  yet  such  sensory  disturbances 
are  not  always  present  with  paralysis  from  cerebral  lesions. 

Cases  of  paralysis  of  the  shoulder  muscles  with  paralysis  of  the 
lower  limb  of  the  same  side  are  reported  in  Hterature.  Bergmark, 
who  was  one  of  the  first  to  write  extensively  on  limited  cortical 
monoplegia,  refers  to  a  case  recorded  by  Oppenheim  in  which  a 
tumor  in  the  center  for  the  leg  gradually  extended  to  the  center 
for  the  arm,  causing  greater  paralysis  of  the  upper  limb  proximally; 
also  to  another  case  in  which  a  cortical  tumor  caused  greater 
paralysis  of  the  hip  and  shoulder  muscles.  In  Sdderbergh's  cases 

1 175 


1 176         SEGMENTAL  CEREBRAL  MONOPLEGIA 

with  paralysis  of  the  shoulder  muscles  there  was  also  paralysis  of 
the  lower  limb  of  the  same  side.  The  investigations  of  Holmes  and 
Sargent  on  thrombosis  of  the  superior  longitudinal  sinus  have  shown 
that  the  center  for  the  shoulder  muscles  is  the  nearest  of  the 
centers  for  the  upper  limb  to  the  centers  for  the  lower  limb, 
although  the  center  for  the  trunk  muscles  intervenes.  In  the  form 
of  paralysis  produced  by  a  lesion  of  the  superior  longitudinal  sinus 
and  well  studied  by  Holmes  and  Sargent,  the  finger  movements  either 
escape,  or  are  weak  for  only  a  short  time  after  an  injury,  and 
rapidly  recover  and  regain  their  normal  power.  The  hand  move- 
ments never  remain  weak  long  except  when  the  sinus  lesion  is 
complicated  by  an  independent  injury  of  the  brain.  The  wrist 
movements,  and  especially  those  of  the  elbow,  are  affected  more 
severely  and  recover  less  rapidly,  while  those  of  the  shoulder  often 
are  disturbed  when  the  more  distal  segments  of  the  limb  escape,  and 
recover  much  less  quickly  when  the  whole  limb  has  been  impli- 
cated. The  paralysis  is  pronounced  in  the  lower  limb,  especially 
in  the  distal  muscles,  and  may  implicate  all  four  limbs. 

I  have  suggested  that  the  easiest  way  to  remember  the  dis- 
tribution of  the  motor  segments  in  the  cortex  is  to  consider  these 
segments  from  above  downward,  as  represented  by  an  inverted 
man  with  the  upper  limbs  extended  beyond  the  head.  We  thus  have 
the  representation  of  the  toes  highest  in  the  cortex,  and  then 
follow  the  centers  for  ankle,  knee,  hip,  trunk,  shoulder,  elbow,  wrist, 
fingers,  and  face. 

The  view  that  Bonhoeflfer  entertained,  viz.,  that  monoplegia 
aflPecting  only  the  shoulder  or  the  elbow  with  escape  of  the  hand 
never  occurs,  is  not  tenable,  as  shown  by  Foerster,  among  others. 
Foerster  described  in  1909  isolated  paralysis  of  the  foot,  of  the 
interossei,  and  of  the  shoulder  and  upper  arm  with  escape  of  the 
hand.  Reich  in  19 13  could  find  no  later  work  on  this  subject  since 
the  publication  of  Foerster's  paper,  and  reported  then  several  cases 
from  Foerster's  service  in  which  the  paralysis  of  cortical  origin 
was  confined  to  a  small  portion  of  a  limb.  A  segmental  representa- 
tion of  the  limbs  in  the  motor  cortex,  as  accepted  by  Munk,  is  now 
established  by  clinical  observation. 

Soderbergh  reported  five  cases  of  cortical  or  subcortical  paralysis 
with  greater  impHcation  of  the  proximal  part  of  the  limb.  Either 


SEGMENTAL  CEREBRAL  MONOPLEGIA         1177 

there  was  complete  loss  of  movement  of  the  shoulder  with  intact 
finger  movements,  or  weakness  of  the  shoulder  movements  with 
intact  finger  and  hand  movements,  or  complete  paralysis  of  shoul- 
der movement  with  weakness  of  finger  movements,  or  paralysis 
of  the  entire  upper  limb,  except  that  there  was  flexion  and  exten- 
sion at  the  elbow  and  hand  with  less  finger  involvement.  Three  of 
the  cases  were  with  brain  tumor,  determined  by  operation  or 
necropsy,  one  was  from  sinus  thrombosis  caused  by  constriction  of 
the  superior  longitudinal  sinus,  and  one  was  from  trauma  of  the 
uppermost  part  of  the  central  convolutions.  He  was  able  to  refer  to 
seventeen  cases  in  19 13  which  showed  the  incorrectness  of  Bon- 
hoeff'er's  contention.  The  infrequency  of  observation,  he  suggests,  is 
probably  because  attention  has  not  been  directed  to  the  subject. 

Dejerine  has  seen  cerebral  monoplegia  confined  to  the  forearm 
and  hand,  and  with  Regnard  has  had  a  case  in  which  the  mono- 
plegia consisted  of  Jacksonian  attacks  and  astereognosis  and 
paralysis  limited  to  the  thenar  and  hypothenar  eminences  and  inter- 
osseous muscles.  A  tumor  was  found  at  the  necropsy  implicating 
the  middle  portion  of  the  central  convolutions.  He  refers  to  cases 
reported  in  which  the  monoplegia  implicated  only  the  toes  and 
foot,  states  he  has  observed  this  type  several  times,  and  says 
a  case  of  this  character  was  reported  by  Ferry  and  Gauducheau. 
Dejerine  regards  the  partial  monoplegia  as  more  frequent  than  the 
total  monoplegia,  and  more  frequent  in  the  upper  than  in  the  lower 
limb. 

The  recent  war  has  given  more  opportunity  for  observance  of 
segmental  cerebral  monoplegia,  which  may  assume  a  sensory  as 
well  as  a  motor  type.  Cestan,  Descomps,  Euzi^re,  and  Sauvage 
report  cases  in  which  convulsions  occurred  in  a  region  of  disturbed 
sensation  of  radicular  type. 

In  the  first  case  they  report  a  lesion  of  the  right  parietal  region  resulting 
from  the  bursting  of  a  shell,  and  the  patient  had  convulsive  movements 
which  began  in  the  left  index  and  middle  fingers  and  extended  to  the 
forearm  and  arm.  The  left  hand  was  a  little  weak,  and  while  the  whole 
left  upper  limb  showed  impaired  sensation,  the  impairment  was  chiefly 
marked  along  the  radial  side  of  the  forearm  and  hand.  Thus  the  con- 
vulsive movements  in  their  commencement  were  in  the  pseudo-radicular 
region  of  disturbed  sensation. 


iiyS         SEGMENTAL  CEREBRAL  MONOPLEGIA 

Their  second  case  was  similar.  A  lesion  of  the  left  parietal  region, 
likewise  caused  by  the  bursting  of  a  shell,  gave  rise  to  sensory  epileptic 
attacks,  consisting  of  paresthesia  in  the  right  upper  limb,  where  objective 
disturbance  of  sensation  was  most  pronounced  in  the  inner  side  of  this 
limb.  In  this  case  convulsive  movements  were  absent. 

The  third  case  was  one  of  lesion  of  the  right  parietal  region,  with  con- 
vulsions beginning  in  the  last  two  fingers  of  the  left  hand  and  disturbance 
of  objective  sensation  predominating  on  the  ulnar  side  of  the  hand  and 
the  external  border  of  the  foot.  The  fourth  case  was  similar. 

These  cases  do  not  prove  that  the  lesion  was  in  the  motor  area, 
producing  irritation  and  convulsions,  but  they  raise  the  interesting 
question  whether  lesions  of  the  parietal  lobe  may  cause  reflexly 
convulsions  beginning  in  the  motor  representation  corresponding  to 
the  sensory;  i.e.,  when  the  lesion  causes  a  sensory  disturbance  of 
the  hand  may  it  reflexly  cause  irritation  of  the  motor  hand  area. 
We  have  one  of  the  best  illustrations  of  the  possibiHty  of  this  in 
the  facial  spasms  associated  with  trifacial  neuralgia  and  produced 
in  the  distribution  of  the  seventh  nerve  by  irritation  of  the  fifth 
nerve. 

In  the  case  reported  by  Parhon  and  Vasiliu  a  soldier  was  injured 
by  a  bullet  in  the  left  parietal  region  and  the  bullet  did  not  enter  the 
brain.  As  a  result  of  this  lesion  a  tremor  like  that  of  Parkinson's  disease 
developed  only  in  the  right  middle,  ring,  and  little  fingers,  and  all 
voluntary  movement  was  lost  in  these  fingers.  Sensation  in  its  various 
forms  was  diminished  only  in  these  three  fingers.  An  operation  revealed  a 
fracture  of  the  internal  table  of  the  skull,  and  the  dura  was  not  opened. 
Some  voluntary  power  returned  in  the  affected  fingers  after  the  opera- 
tion. As  the  authors  point  out,  the  resemblance  to  ulnar  palsy  was 
striking.  They  refer  to  a  case  one  of  them  had  had,  in  which  at  the  beginning 
of  an  apoplectic  attack  paralysis  was  confined  to  the  thumb  and  index 
finger,  was  associated  with  clonic  convulsions  of  the  thumb  and  face, 
and  was  followed  by  brachial  monoplegia. 

The  case  reported  above  is  employed  by  these  authors  to  show 
how  closely  cortical  paralysis  may  simulate  peripheral  nerve  par- 
alysis and  how  closely  the  motor  center  of  a  part  is  related  to  the 
sensory  center  of  the  same  part;  they  do  not  suggest  that  these 
centers  are  identical,  and  in  their  case  the  limitation  of  the  lesion 
could  not  be  determined.   This  case  and  that  of  Dejerine  and 


SEGMENTAL  CEREBRAL  MONOPLEGIA  1179 

Regnard  are  particularly  interesting  in  connection  with  the  first 
and  second  cases  reported  by  me  in  this  paper,  in  which  the  hand 
alone  was  affected  at  first.  The  weakness  of  the  face  in  my  second 
case  was  so  slight  it  could  have  easily  escaped  detection.  Impor- 
tant in  this  connection  is  the  rep>ort  of  a  case  by  Richter. 

The  case  of  paralysis  of  the  right  hand  rep)orted  by  him  was 
one  occurring  during  typhoid  fever  and  was  without  necropsy. 
He  remarks  that  the  finer  details  of  cortical  motor  localization  have 
had  rather  unsatisfactory  demonstration  in  human  pathology,  and 
refers  to  the  three  types  of  cortical  monoplegia  described  by  Oppen- 
heim  in  his  textbook:  the  crural  monoplegia  from  lesion  of  the 
paracentral  lobule  and  upper  third  of  the  anterior  central  convolu- 
tion; the  faciobrachial  type  from  lesion  of  the  middle  portion  of  the 
same  convolution;  and  the  glossolabial  type  from  lesion  of  the  lower 
third  of  this  convolution. 

In  Richter's  patient  paralysis  of  the  right  hand  deveIop>ed  suddenly 
with  paralysis  of  the  right  side  of  the  face,  headache,  and  complete  loss 
of  speech.  He  was  said  to  have  understood  spoken  and  written  words. 
Improvement  began  gradually  after  three  weeks,  especially  in  speech. 
When  examined  about  one  year  after  the  onset  the  lower  part  of  the 
right  side  of  the  face  was  weak.  The  right  upper  limb  was  moved  volun- 
tarily normally  at  the  shoulder  and  elbow,  although  resistance  in  the 
muscles  possibly  was  weakened.  All  voluntary  movement  was  entirely 
lost  in  the  right  wrist  and  fingers.  Electrical  reactions  of  the  hand  were 
normal.  Touch,  pain,  heat  and  cold  sensations  were  diminished  in  the 
right  hand,  and  these  sensations  became  normal  in  the  lower  part  of  the 
forearm.  Speech  was  slightly  affected. 

Richter  believed  that  the  lesion  was  either  an  embolism  or 
hemorrhage  affecting  a  small  part  of  the  motor  cortex. 

Marie  and  L6vy  report  a  case  of  facial  monoplegia  following  a  shell 
wound  of  the  head.  At  first  paralysis  of  the  upper  Hmb  was  associated  with 
the  facial  palsy,  but  the  former  lasted  only  eight  days.  The  facial  palsy 
was  slight,  but  was  of  the  upper  neurone  type.  Marie  and  Foix  have 
reported  several  similar  cases,  with  or  without  anarthria  and  brachial 
paralysis.  Careful  observation  of  such  a  case  ought  to  prevent  any  con- 
fusion with  peripheral  facial  palsy,  by  the  association  with  palsy  of 
another  part,  perhaps  of  short  duration,  and  by  the  type  of  the  facial 
palsy. 


ii8o         SEGMENTAL  CEREBRAL  MONOPLEGIA 

Decidedly  unique  is  the  case  of  double  monoplegia  reported  by 
Regnard,  Mouzon,  and  LafFaille. 

A  woman,  aged  twenty-six  years,  had  paralysis  confined  in  the  right 
upper  limb  to  certain  muscles  of  the  hand  and  wrist.  In  the  right  lower 
limb  certain  muscles  of  the  foot  and  leg  below  the  knee  were  paralyzed, 
but  flexion  and  extension  of  the  leg  at  the  knee  and  movements  of  the 
thigh  were  normal.  The  monoplegias  were  thus  confined  to  the  extremities 
of  the  two  limbs.  Cortical  lesions  were  regarded  as  certain.  The  peripheral 
nerves  could  not  be  aff^ected  on  account  of  exaggeration  of  tendon  reflexes 
of  the  limbs,  Babinski's  sign,  and  absence  of  disturbance  of  sensation.  A 
lesion  of  the  spinal  cord  was  improbable.  The  lesion  was  supposed  to  be 
syphilitic  meningitis,  causing  disseminated  plaques.  In  confirmation  of 
this  opinion  were  sixth  nerve  palsy  and  improvement  under  mercurial 
treatment. 

No  weakness  of  the  face  on  the  side  of  the  weak  hand  was  de- 
tected in  my  fiirst  case  before  the  paralysis  extended  up  the  limb, 
and  one  might  expect  such  weakness  to  occur,  as  several  reported 
cases  have  shown  that  cortical  anesthesia  confined  in  the  upper 
limb  to  the  hand  is  associated  with  cortical  anesthesia  about  the 
mouth  on  the  same  side,  and  slight  weakness  of  the  face  and  tongue 
was  associated  with  the  weakness  of  the  hand  in  my  second  case. 
This  close  association  in  the  cortex  of  the  centers  of  sensation  of  the 
parts  about  the  mouth  and  of  the  hand  would  suggest  a  similar 
close  association  of  the  centers  of  the  motor  innervation  of  these 
parts,  and  the  case  of  Richter  referred  to  above  and  my  second  and 
fourth  cases  are  confirmative  of  this  view. 

In  both  cases  reported  by  Gerstmann  the  disturbance  of  sensa- 
tion was  about  the  mouth  and  in  the  thumb  and  thenar  eminence 
of  the  same  side,  and  the  lesion  was  in  the  opposite  parietal  lobe. 
These,  and  similar  cases  to  which  Gerstmann  refers,  permit  the  con- 
clusion that  the  sensory  center  for  the  mouth  must  be  very  near 
the  sensory  center  for  the  thumb.  Another  justifiable  conclusion 
from  this  case  is  that  pain  and  temperature  sensations  may  be  more 
disturbed  from  lesions  of  the  parietal  lobe  than  other  forms  of  sensa- 
tion, although  parietal  lobe  lesions  are  more  likely  to  disturb  the 
senses  of  position,  passive  movement  and  spacing,  and  stereognosis. 

A  case  similar  to  Gerstmann's  is  reported  by  Camper,  but  it 
differs  in  that  the  anesthesia  was  on  the  ulnar  side  of  the  hand  and 


SEGMENTAL  CEREBRAL  MONOPLEGIA         1181 

forearm,  and  in  this  respect  resembling  the  case  of  Parhon  and 
Vasiliu  already  cited,  but  the  sensory  disturbance  of  the  face  in 
association  with  the  anesthesia  on  the  ulnar  side  of  the  hand  induced 
Gamper  to  conclude  that  two  lesions  occurred,  as  the  centers  affected 
were  not  adjoining. 

In  Popper's  case  a  wound  of  the  parietal  lobe  caused  complete 
loss  of  all  forms  of  sensation  in  all  the  fingers  of  the  opposite  hand, 
with  less  involvement  of  the  thumb,  but  confined  to  the  ends  of  the 
fingers. 

Marie  says  he  has  been  able  to  observe  a  certain  number  of 
brachial  and  crural  monoplegias  from  head  injuries  during  the  war, 
and  that  the  brachial  form  is  more  frequent  than  the  crural.  In  the 
brachial  monoplegias  he  has  almost  always  found  some  signs  of 
implication  of  the  lower  limb.  He  has  observed  motor  and  sensory 
paralysis  confined  to  the  hand  quite  frequently  from  injury  of  the 
Rolandic  region  and  especially  from  injury  of  the  middle  portion 
of  the  ascending  parietal  convolution.  He  calls  these  palsies  mains 
corticales.  There  is  in  these  cases  a  weakness  of  the  hand  movement 
resembling  slight  lesion  of  the  ulnar  nerve  and  superficial  and  deep 
sensory  disturbances  of  variable  intensity  in  the  diff'erent  cases,  and 
disturbance  of  stereognosis  often  pronounced  and  confined  to  the 
radial  or  ulnar  part  of  the  hand.  He  proposed  to  discuss  these  palsies 
more  fully,  but  I  have  not  found  anything  further  than  this  brief 
statement  from  his  pen. 

The  first  case  which  I  report  is  one  in  which  a  paralysis  confined  to 
the  left  hand  was  said  by  the  patient  to  have  developed  rapidly  and  to  have 
existed  a  little  more  than  three  weeks,  and  was  chiefly  in  the  ulnar  and 
median  nerve  distributions.  The  man  had  been  working  overtime  as  a 
carpenter  in  the  necessity  that  existed  in  preparing  quarters  for  the 
drafted  men.  It  was  a  period  of  great  national  stress.  As  sensory  dis- 
turbance of  a  hysterical  character  was  present  at  the  first  examination 
and  disappeared  rapidly  under  psychotherapy,  it  was  thought  at  first 
that  the  paralysis  of  the  hand  might  be  hysterical,  and  under  the  treat- 
ment by  psychotherapy  and  the  stimulus  thereby  given  to  employ  the 
motor  power  of  the  hand  to  the  utmost  the  man  seemed  to  gain  pwwer. 
He  came  to  the  dispensary  several  times,  but  the  power  of  the  hand  never 
increased  beyond  the  slight  improvement  produced  at  first.  It  became 
evident  to  me  that  the  paralysis  was  organic,  and  as  he  had  pressed  the 


ii82         SEGMENTAL  CEREBRAL  MONOPLEGIA 

left  wrist  with  much  force  against  the  plane  in  long-continued  labor  it 
seemed  possible  that  I  might  have  to  deal  with  a  pressure  palsy.  On  account 
of  many  patients  coming  to  the  dispensary  and  the  difficulty  of  examining 
them  properly  with  our  depleted  medical  staff,  the  electrical  examination 
was  not  made.  It  probably  would  have  revealed  no  changes,  as  the  paralysis 
was  cerebral.  The  later  development  of  the  case  permitted  the  diagnosis  of 
tumor  of  the  motor  area  of  the  brain,  and  operation  was  performed  by 
Major  C.  H.  Frazier  with  confirmation  of  this  diagnosis. 

In  the  second  case  the  right  hand  alone  was  weak,  the  sense  of  position 
was  greatly  impaired,  and  stereognosis  was  lost  in  this  hand.  The  muscles 
of  the  right  corner  of  the  mouth  were  a  little  weak  and  the  tongue  when 
almost  fully  protruded  deviated  a  little  to  the  right.  Convulsions  had 
begun  in  the  right  hand  in  the  onset  of  symptoms  and  beginning  papille- 
dema was  found.  Dr.  A.  C.  Wood,  at  my  request,  exposed  the  left  motor 
parietal  region,  and  a  small  tumor  was  found  in  the  center  for  the  upper 
limb,  having  the  appearance  of  a  tuberculous  growth  microscopically.  A 
few  small  plaques  were  found  in  the  parietal  lobe. 

The  only  indication  of  implication  of  the  right  lower  limb  was  some 
exaggeration  of  the  tendon  reflexes  of  this  limb,  but  Babinski's  reflex  was 
not  obtained.  As  the  fibers  from  the  cortical  center  for  the  lower  limb 
pass  beneath  the  cortex  of  the  center  for  the  upper  limb  on  their  way 
to  the  inner  capsule,  it  was  evident  that  the  lesion  could  not  extend  deeply 
into  the  brain,  as  otherwise  there  surely  would  have  been  a  Babinski 
reflex  and  some  weakness  of  the  lower  limb.  The  early  Jacksonian  con- 
vulsions also  suggested  that  the  lesion  was  cortical. 

In  the  third  case  the  possibility  of  hysteria  also  had  to  be  considered. 
The  patient  had  recently  completed  a  beautiful  home  and  had  lost  his 
wife  about  three  months  later.  The  first  sign  of  weakness  was  detected 
during  the  funeral  of  his  wife,  when  he  stubbed  the  toes  of  his  right  foot 
in  going  upstairs.  As  he  was  an  emotional  man,  the  ground  seemed  well 
prepared  for  a  hysterical  attack.  At  my  first  examination,  about  three 
weeks  after  the  beginning  of  his  symptoms,  there  was  slight  right  hemi- 
paresis,  which  had  developed  very  gradually  with  complete  paralysis  of 
the  muscles  of  the  right  shoulder,  while  the  grasp  of  the  right  hand  was 
about  as  good  as  that  of  the  left,  although  stereognosis  and  senses  of  posi- 
tion and  passive  movement  were  lost  in  the  right  hand.  Within  a  few 
days  the  extension  of  the  paralysis  downward  in  the  right  upper  limb 
indicated  a  cerebral  lesion,  and  the  further  development  of  the  case  per- 
mitted the  diagnosis  of  brain  tumor.  Operation  was  not  desired  by  the 
patient  or  his  relatives  and  a  necropsy  could  not  be  obtained. 

In  the  fourth  case  a  paralysis  of  the  right  side  of  the  tongue,  of  the 


SEGMENTAL  CEREBRAL  MONOPLEGIA  1183 

lower  part  of  the  right  side  of  the  face,  and  of  the  right  hand,  with 
indistinctness  of  speech,  developed  during  sleep  in  a  man  thirty-seven 
of  age.  Movement  at  the  right  elbow  and  shoulder  was  normal.  Much 
improvement  occurred  in  the  condition  within  three  weeks.  The  lesion 
probably  was  in  a  small  branch  from  the  middle  cerebral  artery  supply- 
ing the  motor  cortex  affected. 

I  have  no  doubt  many  similar  cases  will  be  observed  when  attention 
is  paid  to  the  subject.  Lack  of  space  prevents  the  publishing  of  the  notes 
of  these  cases  in  detail. 

BIBLIOGRAPHY 

Bergmark,  "Review  of  Neurology  and  Psychiatry,"  19 10,  199. 

Holmes  and  Sargent,  Brit.  M.  J.,  October  2,  1915,  493. 

Spiller,  Progr.  Med.,  September,  1916,  333. 

Reich,  Deutsche  Ztscbr.  J.  Nervenb.,  1913,  XLVI,  446. 

SSderbergh,  Deutsche  Ztschr.  J.  Nervenh.,  XLIX,  253. 

Dejerine,  "Semiologie  des  affections  du  syst^me  nerveux,"  2d  Ed.,  255. 

Cestan,  Descomps,  Euzi^re,  and  Sauvage,  Revue  neurologique,  April  and 

May,  191 7,  235. 
Parkon  and  Vasiliu,  Rev.  neurol,  April  and  May,  191 7,  156. 
Richter,  Neurologisches  Centralblatt,  July  i,  191 8,  450. 
Marie  and  L6vy,  Rev.  neurol.,  November  and  December,  19 16,  513. 
Marie,  Rev.  neurol.,  November  and  December,  19 16,  617. 
Regnard,  Mouzon,  and  LafFaille,  Rev,  neurol,  June  30,  1914,  838. 
Gerstmann,  Neurol.  Centralbl,  July  i,  1918,  434. 
Gamper,  Monatsschr.  J.  Psychiat.  u.  Neurol.,  January,  1918,  21. 
Popper,  Neurol.  Centralbl.,  July  i,  19 18,  447. 


THE  RELATION  OF  THYROID  SECRETION  TO  THE 
CONDITION  OF  THE  SKIN— AND  INCIDENT- 
ALLY TO  OLD  AGE 

By  M.  Allen  Starr,  M.D.,  New  York 

^^S  old  age  advances,  the  condition  of  the  skin,  nails,  and  hair 
A^L  undergoes  certain  changes.  The  skin  becomes  dry  and  scaly, 
jL  JLis  liable  to  wrinkle  and  crack,  especially  when  exposed  to 
cold  air;  and  the  normal  secretion  of  sweat  is  diminished,  even 
under  the  stimulus  of  exertion  and  of  heat.  The  nails  become  ridged 
or  striated,  very  hard,  even  horny,  and  very  brittle.  The  hair  loses 
its  glossy  appearance,  is  dry,  breaks  easily,  and  is  liable  to  fall  out, 
leaving  the  head  bald. 

These  changes  have  been  observed  quite  uniformly  in  patients 
suffering  at  any  age  from  myxedema  or  milder  states  of  hypo- 
thyroidism. It  seems,  therefore,  as  if  the  conclusion  might  be  justified 
that  in  old  age  they  are  due  to  a  lack  of  thyroid  activity.  Hence  it 
has  been  my  practice  in  recent  years  to  prescribe  small  amounts  of 
thyroid,  not  more  than  one  grain  of  the  Burroughs  &  Welcome 
extract,  in  divided  doses,  in  a  day,  to  all  those  persons  above  the 
age  of  fifty,  who  show  any  of  these  changes  in  the  skin,  nails,  and 
hair. 

It  has  been  interesting  to  notice  that  in  all  cases  under  the  use 
of  thyroid  these  conditions  of  the  skin,  nails,  and  hair  have  promptly 
subsided,  and  have  disappeared,  not  returning,  unless  the  thyroid 
treatment  is  stopped.  Incidentally  it  has  been  noticed  that  during 
such  treatment  the  pulse  tension,  if  at  all  abnormally  high,  has 
diminished,  not  infrequently  from  15  to  20  mm. 

It  is  not  unusual  for  patients  to  mention,  spontaneously,  that 
they  feel  more  active,  mentally  as  well  as  physically,  while  taking 
thyroid.  This  is  not  surprising,  in  view  of  the  well-known  mental 
alertness  of  persons  suffering  from  Graves*  disease.  It  has  been 
observed  that  it  also  tends  to  diminish  depression  and  insomnia. 

1 184 


THYROID  SECRETION  AND  THE  SKIN         1185 

The  conclusion,  therefore,  may  be  reached  that  some  of  the  con- 
ditions supposedly  due  to  old  age  are  actually  due  to  a  diminu- 
tion in  the  activity  of  the  thyroid  gland,  and  that  consequently 
they  may  be  obviated  or  removed  by  the  constant  use  of  thyroid 
extract  as  age  advances. 


RELATION   OF  ACUTE   INFECTION  TO   DIABETES 
By  Alfred  Stengel,  M.D., 

Professor  of  Medicine,  University  of  Pennsylvania 

IT  has  been  found  by  various  authors  that  (I)  acute  infections 
with  fever  may  occasion  some  disturbance  of  the  carbohydrate 
tolerance  with  increase  of  blood-sugar  and  transient  glycosuria; 
that  in  these  circumstances,  the  administration  of  glucose  is  fol- 
lowed by  excretion  of  sugar  in  varying,  sometimes  considerable, 
amounts  (alimentary  glycosuria);  (II)  that  occasionally  diabetes, 
temporary  or  permanent,  may  follow  acute  infections,  and  (III) 
that  infectious  diseases  occurring  in  diabetic  persons  increase  the 
disturbance  of  carbohydrate  metabolism  and  precipitate  other  un- 
favorable conditions,  notably  acidosis;  it  has,  however,  been  claimed 
by  some  writers  that  diabetes  is  favorably  influenced  by  the  inter- 
vention of  an  acute  infection. 

I.  Though  clinical  observers  had  for  a  long  time  known  that 
glycosuria  occasionally  appears  in  the  course  of  infectious  diseases, 
the  direct  demonstration  that  the  carbohydrate  tolerance  is  di- 
minished and  blood-sugar  increased  in  febrile  infections  seems  first 
to  have  been  made  by  Poli,  (i)  who  administered  glucose  in  amounts 
of  from  100  to  150  grams  to  patients  who  were  suffering  from 
scarlatina,  diphtheria,  septicemia,  tonsillitis,  and  pneumonia,  and 
found  in  many  of  them  definite  glycosuria.  In  two  cases  of  pneu- 
monia, the  amount  of  sugar  in  the  urine  was  3  and  4  per  cent  re- 
spectively; and  7  and  8  per  cent  of  the  total  ingested  sugar  was 
eliminated  through  the  urine.  Later  Liefmann  and  Stern  (2) 
reported  the  finding  of  marked  increase  in  the  amount  of  blood- 
sugar  in  febrile  conditions  (pneumonia)  without  any  glycosuria. 
They  made  no  attempts  to  repeat  Poli's  observations.  HoIIinger  (3) 
also  found  high  blood-sugar  figures  in  cases  of  pneumonia  and  other 
febrile  conditions.  Tachau  (4)  also  reported  the  finding  of  consider- 
able hyperglycemia  in  febrile  aff'ections,  and  was  able  to  increase 
the  amount  of  blood-sugar  notably,  by  the  administration  of  sugar, 

1 186 


ACUTE  INFECTION  AND   DIABETES  1187 

without  precipitating  glycosuria.  Previous  to  these  observations 
Roger  and  Bouchard  (5)  found  that  in  experimental  anthrax,  after 
twenty-four  or  forty-eight  hours,  the  blood  of  the  animals  contained 
from  0.224  to  0.297  per  cent  of  sugar,  while  the  serous  fluids  in  the 
neighborhood  of  the  injections  were  also  heavily  loaded  with  sugar. 

It  seems  evident  from  these  observations  that  a  moderate  or 
considerable  hyperglycemia  occurs  in  the  course  of  various  in- 
fections, and  that  the  administration  of  sugar  may  produce  ali- 
mentary glycosuria  more  readily  than  in  normal  individuals.  These 
conditions  are  apparently  frequent,  though  transient,  in  infections. 
How  often  they  lead  to  more  permanent  results  must  be  estabhshed 
from  clinical  observations  in  persons  recovered  from  infections. 

II.  A  complete  review  of  the  literature  bearing  upon  the  occur- 
rence of  glycosuria  or  diabetes  during  or  after  infections  would 
not  be  especially  profitable,  because  most  of  the  publications  date 
from  periods  when  accurate  clinical  and  chemical  studies  were 
not  available.  It  will,  however,  be  useful  to  refer  to  some  of  the 
readily  accessible  literature  to  show  how  frequently  and  in  how 
many  varied  forms  of  infection  sugar  has  been  detected  in  the 
urine,  though  it  will  at  the  same  time  be  noted  that  very  few  of  the 
reported  cases  were  followed  to  their  conclusion.  It  is  imp>ossibIe  to 
determine  how  often  there  was  but  an  ephemeral  or  transient  gly- 
cosuria, and  how  often  an  actual  diabetes  occurred.  The  emphasis 
laid  upon  the  degree  of  glycosuria  by  older  writers  as  determining 
the  existence  of  actual  diabetes  seems  without  doubt  to  have  been 
unwarranted.  Severe  diabetes  may  begin  and  perhaps  continue  with- 
out marked  glycosuria,  and,  on  the  other  hand,  considerable  amounts 
of  sugar  may  be  excreted  in  cases  of  mild  diabetes,  or  possibly 
of  transient  glycosuria.  It  is  not  improbable  that  some  and  perhaps 
many  of  the  cases  of  "glycosuria"  met  with  during  and  after  acute 
infections,  if  seen  at  intervals  later,  might  later  have  turned  out  to 
be  actual  diabetes.  Some  such  explanation  is  necessary  to  elucidate 
the  fact  that  careful  students  of  diabetes  have  so  rarely  been  able 
to  trace  cases  back  to  definite  infections,  if  this  origin  is,  indeed, 
a  common  one;  and  there  seems  good  reason  to  believe  that  it  may 
be,  in  view  of  the  fact  that  certain  observers  have  found  undoubted 
instances  and  that  disease  of  the  pancreas  is  a  complication  that 
may  readily  occur  in  infectious  diseases.   Naunyn,  Lepine,  von 


ii88  ACUTE  INFECTION  AND  DIABETES 

Noorden,  Kleen,  Allen,  and  Joslin  refer  to  the  probable  etiological 
relationship,  but  say  little  of  their  personal  observations,  or  while 
admitting  the  possibihty,  doubt  the  accuracy  of  many  of  the 
reports.  Von  Noorden  (6)  says,  "In  most  of  these  cases  the  causal 
relation  between  the  two  diseases  is  very  doubtful,  furnishing  an 
instance  of  the  confusion  of  post  hoc  and  propter  hoc.'^  After  reciting 
a  case  in  which  diabetes  seemed  to  have  followed  influenza,  but 
was  later  found  to  have  existed  previously,  he  continues,  "But  it 
cannot  be  denied  that  acute  infectious  diseases  may  actually  cause 
diabetes."  Naunyn  evidently  accepted  many  of  the  older  reports 
without  expressing  his  conviction  very  clearly.  Lepine  is  manifestly 
skeptical.  Joslin  (7)  says:  "The  influence  of  infections  has  received 
considerable  attention  of  late.  In  only  a  few  instances  have  I  been 
able  to  associate  infectious  diseases  with  diabetes;  in  fact,  in  only 
28  cases  of  my  series.  When  one  considers  the  frequency  of  infectious 
diseases  in  a  community  and  the  rarity  with  which  diabetes  develops 
after  the  same,  one  is  not  inclined  to  assign  great  importance  to 
infections."  Further  on  he  adds,  "I  certainly  remain  open  minded 
on  it."  Though  I  am  far  from  convinced  that  infection  is  the  all- 
important  factor,  I  am  much  impressed  by  the  occasional  striking 
cases  that  have  come  under  my  observation,  and  can  readily  believe 
that  the  connection  may  be  difficult  of  demonstration  because  the 
development  of  the  disease  is  frequently  quite  gradual.  In  this 
particular  diabetes  resembles  arthritis,  chronic  anemia,  and  nephri- 
tis, conditions  which  are  recognized  as  occurring  insidiously  after 
preceding  infections  or  as  a  result  of  chronic  focal  infections. 

I  have  purposely  confined  the  scope  of  my  discussion  to  acute 
infections;  for  this  reason,  in  the  references  that  follow,  syphilis 
has  been  omitted,  though  much  might  be  said  on  this  subject. 
Naunyn  refers  to  it  extensively  in  his  book. 

Malaria.  According  to  Kleen,  (8)  Peter  Frank  and  Sydenham 
mentioned  the  association  of  diabetes  with  malaria  (9).  Burdel  (10) 
makes  a  remarkable  report  showing  the  frequency  of  glycosuria  in 
association  with  malaria.  Among  134  quotidian  fevers,  glycosuria 
occurred  in  25;  among  122  tertian  cases,  in  17;  among  78  quartan 
cases,  in  11;  among  40  of  malarial  cachexia,  in  32;  among  11  per- 
nicious malarial  fevers,  in  3.  The  amount  of  sugar  was  small  and 
usually  below  0.5  per  cent.  His  method  of  determination  is  not 


ACUTE  INFECTION  AND   DIABETES  1189 

mentioned.  Verneuil  (11)  confirms  Burdel's  findings,  and  reports 
glycosuria  in  17  of  no  cases  of  malaria  without  cachexia  and  in 
76  of  100  cases  with  cachexia.  Calmette  (12)  found  sugar  in  5  of 
41  malarial  soldiers,  and  Rumpf  (13)  in  13  of  100  cases  of  malaria. 

These  extraordinary  figures  have  not  been  confirmed  by  others. 
Lepine  (14)  and  Naunyn  question  the  accuracy  of  the  observations 
and,  at  all  events,  deny  any  relationship  between  such  glycosuria 
and  diabetes.  Laveran  (15)  states  that  diabetes  is  rare  where  malaria 
is  endemic,  and  Dieu  (16)  notes  that  diabetes  is  not  more  frequent 
in  those  parts  of  Algeria,  where  almost  everybody  has  malarial 
infection,  than  in  France. 

Cholera.  Heintz  and  Samjoe  (17)  first  noted  the  occurrence  of 
glycosuria  in  severe  cases  of  cholera.  Huppert  (18)  found  that  the 
sugar  appeared  as  the  patients  began  to  recover  and  when  the  urine 
increased  after  the  preliminary  anuria.  Neither  he  nor  Gubler  (19) 
saw  the  amount  of  sugar  above  i  per  cent.  Usually  the  excretion  of 
sugar  is  very  transient,  clearing  up  after  two  or  three  days.  Naunyn 
states  that  the  development  of  an  actual  diabetes  mellitus  has 
never  been  observed. 

Dipbtberia.  Binet  (20)  found  sugar  in  many  severe  cases  of 
diphtheria,  and  Hibbard  and  Morrissey  (21)  also  found  transient 
glycosuria  very  common  in  severe  and  usually  present  in  fatal  cases. 
Occasionally  it  followed  the  antitoxin  injection,  and  they  considered 
it  the  result  of  the  toxemia  and  not  of  the  asphyxia  accompanying  the 
disease. 

Mumps.  Harris  (22)  reported  a  severe  case  of  glycosuria  fol- 
lowing mumps,  and  assumed  that  the  pancreas  was  aff'ected.  Gar- 
rod  (23)  also  reports  a  series  of  cases  of  mumps  with  pancreatitis, 
in  some  of  which  glycosuria  or  transient  diabetes  occurred.  Lepine, 
however,  states  that  while  a  number  of  authors  have  reported 
instances  of  pancreatitis  in  association  with  mumps  (24),  diabetes 
was  not  found  as  a  sequel,  and  he  also  mentions  the  fact  that  pan- 
creatitis has  been  observed  in  typhoid  fever  without  such  a  sequel. 

Scarlatina,  Measles,  Pertussis,  etc.  In  scarlatina,  Zinn  (25)  and 
Stern  (26);  in  measles,  Stern  (27),  Barlow,  Bordier,  and  others; 
and  in  whooping  cough,  Thomson  (28)  reported  the  occurrence  of 
glycosuria  in  occasional  cases.  It  has  also  been  found  in  vaccinia, 
malignant  pustule,  variola,  and  in  other  infections. 


1 190  ACUTE  INFECTION  AND   DIABETES 

Furunculosis  and  Minor  Injections.  The  association  of  diabetes 
with  furunculosis  has  been  frequently  discussed,  and  some  of  the 
observers  thought  that  the  glycosuria  was  the  result  of  the  infection. 
The  leading  authorities,  however,  unanimously  regard  the  furuncular 
disease  as  the  consequence  of  pre-existing  diabetes,  as  this  occur- 
rence is  very  commonly  observed  in  known  diabetics.  Somewhat  the 
same  view  is  held  regarding  other  minor  local  infections — in  the 
oral  cavity,  about  the  eyes,  in  the  skin,  etc. 

Pneumonia.  Rosenberger  (29),  Lion  (30)  and  a  number  of  other 
authors  refer  to  glycosuria  in  this  disease. 

Influenza.  Rumpf  (31)  found  an  apparently  initial  history  of 
influenza  in  15  cases  among  100  diabetics.  Holsti  (32)  and  Kleen 
(33)  also  refer  to  cases. 

The  list  of  infectious  diseases  with  which  glycosuria  has  been 
found  associated  is  by  no  means  completed  in  the  above  tabulation. 
Occasional  occurrences  in  other  conditions,  such  as  erysipelas,  sep- 
ticemia, hydrophobia,  rheumatism,  erythema  nodosum,  and  gastro- 
intestinal infections,  might  be  added. 

It  will  be  found  from  a  review  of  this  literature  that  so  far  as 
can  be  learned  from  the  reports,  the  cases  recorded  have  been  with 
few  exceptions  instances  of  temporary  glycosuria  accompanying 
the  infection  named,  and  probably  occurring  only  during  the  febrile 
period  of  the  disease.  In  but  a  few  of  the  reported  cases  has  the 
history  been  followed,  and  the  development  of  a  lasting  diabetes 
established. 

In  my  own  cases,  to  which  I  shall  presently  refer,  the  fact  that, 
in  association  with  or  following  acute  infections,  continuous  gly- 
cosuria and  more  or  less  marked  acidosis  occurred,  indicates  that 
not  merely  a  reduced  carbohydrate  tolerance,  but  actual  diabetes, 
was  developed.  The  possible  occurrence  of  a  pancreatic  lesion  as  a 
result  of  the  infection  will  be  considered  later. 

The  following  cases,  selected  from  my  series  of  slightly  over  200 
cases  of  diabetes,  though  few  in  number,  seemed  striking  enough 
to  be  placed  on  record.  In  each  of  them  the  patient  was  under 
observation  long  enough  to  determine  that  there  was  an  actual 
diabetes  and  not  a  transient  glycosuria.  It  is  quite  certain  that 
none  was  diabetic  before  the  occurrence  of  the  infection  which 
seemed  to  have  precipitated  or  caused  the  diabetes.  Probably  15  or 


ACUTE  INFECTION  AND   DIABETES  1191 

20  other  cases  might  have  been  added  had  I  included  instances  in 
which  the  history  seemed  to  date  from  some  acute  infection,  but 
in  which  the  antecedent  health  of  the  patient  was  not  certain. 

Case  I.  Severe  diabetes  following  antrum  infection  and  facial  ery- 
sipelas; apparent  complete  recovery;  4^  years  later,  acute  recurrence 
following  influenza.  Dr.  W.  W.  S.,  aged  twenty-four  years,  was  admitted 
to  the  University  Hospital  March  7,  19 14,  with  the  evidences  of 
severe  diabetes.  He  had  had  measles  in  childhood,  some  digestive  dis- 
turbance prior  to  appendectomy  at  thirteen  years,  and  typhoid  fever  at 
seventeen.  Later  he  suffered  from  repeated  attacks  of  tonsillitis.  On  No- 
vember 15,  19 1 3,  his  tonsils  were  removed;  November  22d,  developed 
uveitis  in  his  right  eye,  which  continued  for  some  time;  December  2d,  was 
seized  with  an  acute  febrile  condition  (grippe?)  which  was  followed  on 
December  loth  by  infection  of  the  right  antrum.  From  that  date  to  De- 
cember 17th,  temperature  ranged  from  102^^°  to  105°;  December  17th, 
developed  facial  erysipelas,  temperature  from  December  17th  to  December 
24th,  103^°  to  io6f°.  December  25th,  temperature  fell  to  normal.  He 
was  profoundly  prostrated  after  the  attack.  Early  in  January,  1914,  slight 
increase  in  appetite,  thirst,  and  urinary  excretion  were  noted,  but  attrib- 
uted to  his  recent  illness  and  beginning  convalescence.  February  24th, 
sudden  digestive  disturbance  and  excessive  polyuria — 16,000  c.c.  Dis- 
tressing dryness  of  the  mucous  membranes  and  the  f)oIyuria  led  to  urinary 
examination  and  the  discovery  of  enormous  glycosuria. 

During  his  last  two  years  as  a  medical  student  (1912  and  1913),  he 
had  been  one  of  Prof.  A.  E.  Taylor's  "Food  Squad,"  and  had  made  daily 
examinations  of  his  urine.  Nothing  abnormal  was  detected.  During  the 
acute  illness  (from  November  27th  to  December  24th)  he  was  under  the 
care  of  my  assistant,  the  late  Dr.  F.  H.  Klaer,  who  examined  his  urine 
several  times.  One  complete  record  was  preserved,  which  showed  a  specific 
gravity  of  1.009,  *icid  reaction,  a  trace  of  albumin,  no  sugar,  no  casts. 

On  admission  (March  7,  19 14)  he  was  exceedingly  emaciated  (weight 
123  pounds,  normal  160  pounds),  the  skin  and  mucous  membranes  of  the 
mouth  were  dry,  there  was  a  strong  odor  of  acetone,  perceptible  even  at  a 
distance.  On  account  of  the  evident  acidosis  the  patient  was  kept  upon  a 
diet  fairly  liberal  in  carbohydrates  and  was  given  moderate  amounts  of 
alcohol.  During  this  period  the  polyuria  was  pronounced,  and  the  quantity 
of  sugar  and  acetone  bodies  excreted  were  excessive.  After  five  days  the 
diet  was  considerably  restricted,  but  some  carbohydrate  was  allowed  and 
the  alcohol  was  continued.  The  amount  of  fat  permitted  was  far  in  excess 
of  what  would  be  allowed  at  the  present  day.  Despite  this  fact,  the  evi- 


1 192  ACUTE  INFECTION  AND   DIABETES 

dences  of  acidosis  diminished  after  a  primary  increase  lasting  a  few  days. 
There  was  at  the  same  time  a  rapid  falling  off  in  the  degree  of  glycosuria. 
The  patient  became  sugar- free  on  April  14th,  and  the  acidosis  was  reduced 
to  negligible  proportions  soon  afterward.  The  amount  of  blood-sugar 
remained  distinctly  higher  than  normal  for  some  months  after  the  disap- 
pearance of  the  glycosuria  and  ketonuria,  but  then  fell  to  normal.  During 
the  time  the  patient  was  in  the  hospital  his  weight  increased  rather  rapidly, 
and  he  had  gained  14  pounds  at  the  time  when  he  became  sugar-free. 
Subsequently  the  gain  was  more  gradual  up  to  the  time  of  his  recovery, 
which  occurred  several  months  later. 

(At  the  time  the  patient  came  under  observation,  we  were  unfamiliar 
with  Allen's  methodical  treatment,  and  practiced  fasting  only  as  a  pre- 
liminary to  von  Noorden's  oatmeal  treatment  when  this  seemed  indicated. 
Had  this  case  been  treated  by  the  methods  of  to-day,  I  have  no  doubt  the 
glycosuria,  as  well  as  the  acidosis,  would  have  disappeared  much  more 
speedily.) 

From  April  14,  1914,  until  some  time  in  December,  191 8,  the  patient 
remained  sugar-free.  He  gradually  increased  the  amounts  of  carbohydrates 
in  his  diet,  and  except  for  restriction  of  sugar  was  using  the  diet  of  average 
normal  persons.  Late  in  19 14  he  resumed  medical  practice,  and  during 
19 1 7  and  19 1 8  was  very  active.  In  the  fall  and  early  winter  of  19 18  his 
work  increased  enormously  on  account  of  the  influenza  epidemic  and  war 
work  in  several  industrial  plants  in  which  he  was  engaged  as  physician. 

In  December  he  himself  fell  a  victim  to  influenza,  the  attack  being 
fortunately  mild;  but  immediately  his  glycosuria  recurred  and  other 
symptoms  (polyuria,  emaciation)  indicated  a  return  of  his  previous  con- 
dition. Readmitted  to  the  hospital,  December  10,  19 18.  There  was  little 
evidence  of  acidosis,  but  marked  increase  in  the  blood-sugar  and  decided 
glycosuria.  Within  forty-eight  hours  under  a  carbohydrate-free  diet  with 
moderate  amounts  of  fat,  the  glycosuria  disappeared,  but  the  blood-sugar 
did  not  return  to  normal  for  one  month. 

Case  II.  Excessive  glycosuria  and  severe  polyuria  occurring  in  the 
course  of  scarlet  fever.  No  evidence  of  acidosis  or  other  indications  of 
severe  diabetes.  Glycosuria,  however,  obstinate.  Death  from  meningitis. 
Miss  E.  A.  S.,  aged  twenty-five,  a  pupil  nurse  at  the  University  Hospital, 
an  exceptionally  athletic  young  woman  (champion  swimmer,  canoeist, 
etc.)  had  been  in  perfect  health  until  the  onset  of  a  severe  attack  of  scarlet 
fever  which  began  about  October  i,  1907.  She  was  sent  to  the  Municipal 
Hosiptal  for  isolation  and  treatment.  While  convalescent  from  the  scar- 
latina, polyuria  developed  and  glycosuria  was  discovered  on  October  i6th. 
From  this  date  until  her  discharge  from  the  Municipal  Hospital  (November 


ACUTE  INFECTION  AND   DIABETES 


"93 


29th)   marked  polyuria  and  glycosuria  continued.   Daily  examinations 
showed  quantities  of  urine  ranging  from  1200  c.c.  to  3900  c.c;  specific 


Diet 

Amount 
Urine 

Sp.  Gr. 

Glu- 
cose 

Total 

N. 

Am- 
monia 

N. 

Ke- 
tones" 

Plasma 
CO, 

Blood 
Sugar 

3-8-14 
Liberal 

9050  C.C. 

1031 

576 

— 

42-9 

3-9-14 
Liberal 

7600  cc. 

1033 

512 

— 

39.3 

3-10-14 
Liberal 

7900  cc. 

1030 

445 

— 

39.4 

3-11-14 
Liberal 

7240  cc. 

1033 

457 

— 

38-2 

3-12-14 
Restricted 

4220  cc. 

1030 

140 

— 

45-9 

3-13-14 

4020  c.c 

1025 

90.2 

— 

47-75 

3-26-14 

2050  cc 

1029 

61 

— 

— 

3-30-14 

1630  cc 

1035 

22 

11-2 

30 

4-  7-14 

1450  cc 

1035 

45 

13-8 

2  9 

4-14-14 

950  cc. 

1029 

0 

— 

— 

4-27-14 

830  cc 

1028 

0 

8-4 

16 

6-11-14 

— 

— 

0 

8-6 

18 

0  118« 

10-24-14 

— 

— 

0 

— 

19 

0  130 

1-23-lS 

— 

— 

0 

— 

015 

0  100 

Re- 
admission 
12-10-18 
full  diet 

2160  c.c 

1  032 

102  3 

14  5 

0  69 

58% 

0  26 

12-12-13 
carbo- 
hydrate- 
free  diet. 

12-13-18 
carbo- 
hydrate- 
free  diet. 

1270  cc 

1021 

trace 

12-14-18 
carbo- 
hydrate- 
free  diet. 

1770  cc 

1  019 

1-  2-19 
carbo- 
hydrate- 
free  diet. 

1800  cc 

1  018 

0  17 

1-10-19 
carbo- 
hydrate- 
free  diet. 

0  10 

*  Ketones  are  expressed  in  terms  of  acetone. 

*  Earlier  records  (much  higher)  have  been  lost. 

gravities  from  1.030  to  1.055;  and  sugar  in  amounts  from  50  to  280  grams 
in  the  twenty-four  hours.  I  received  no  report  regarding  diacetic  acid,  but 


1 194  ACUTE   INFECTION  AND   DIABETES 

the  fact  that  there  was  none  after  she  came  under  my  observation  (No- 
vember 30  et  seq.)  and  that  her  physical  condition  did  not  in  any  way 
suggest  the  existence  of  an  acidosis,  leads  me  to  believe  there  had  been  none 
prior  to  that  time.  During  December,  1907,  under  strict  dieting  the  sugar 
disappeared  rather  quickly,  but  it  recurred  very  promptly  after  an  attempt 
to  increase  the  amount  of  carbohydrates.  A  second  course  of  strict  dieting 
again  succeeded  in  rendering  the  urine  sugar-free.  A  few  weeks  later  the 
patient  tried  to  resume  her  work  as  a  pupil  nurse  (being  then  of  necessity 
on  a  mixed  diet),  but  the  glycosuria  promptly  reappeared.  During  all  of 
this  time  the  patient  appeared  in  the  best  of  health  as  far  as  external 
appearance  was  concerned.  Whatever  loss  of  weight  resulted  from  the 
scarlet  fever  had  been  regained  before  she  came  under  my  care  and  to  all 
appearances  she  was  in  robust  health.  After  a  two  weeks'  trial  it  was  evi- 
dent that  continuance  of  her  nursing  course  was  inadvisable,  and  the  patient 
returned  home  to  rest  and  strictly  regulate  her  diet.  Reports  were  sent  to 
me  at  intervals,  but  I  suspected  that  the  glycosuria  was  only  intermittently 
under  control.  In  November,  1908,  she  returned  to  Philadelphia,  and  I 
found  that  the  glycosuria  was  as  pronounced  as  ever.  Very  shortly  after 
this  date  she  was  persuaded  to  accept  a  minor  position  in  a  theatrical 
company,  and  I  subsequently  learned  that  she  was  taken  acutely  ill  in 
Boston  and  died  in  February,  1909.  Through  the  kindness  of  Dr.  Joslin, 
some  of  the  facts  of  her  fatal  illness  were  communicated  to  me  by  Dr. 
Hunter,  who  reported  that  Miss  S.  had  been  taken  ill  quite  suddenly 
with  sore  throat  and  fever.  When  he  saw  her  a  few  hours  later  the  tempera- 
ture was  99/^°  and  the  pulse  rate  90;  there  was  severe  dyspnea  and  typical 
laryngismus  stridulus.  Subsequently  she  developed  a  stuporous  and  then 
an  unconscious  condition,  with  subnormal  temperature  and  rising  pulse 
rate.  Finally,  unequal  pupils,  retraction  of  the  head,  conjugate  deviation 
of  the  eyes,  and  some  spasticity  of  the  muscles  of  the  legs  suggested  the 
diagnosis  of  cerebrospinal  meningitis.  The  patient  died  within  thirty-six 
hours  of  the  onset.  A  specimen  of  urine  showed  albumin  and  casts  and  an 
abundance  of  sugar,  but  no  mention  was  made  of  diacetic  acid  or  of  any 
indications  of  acidosis.^ 

Case  III.  Mild  diabetes  following  "grippe."  Rapid  disappearance  of 
symptoms  under  treatment.  Dr.  J.  C.  C,  age  thirty-seven  years,  male, 
admitted  to  hospital  on  January  29,  1916.  Dr.  C.  had  felt  perfectly  well 

*  When  this  case  came  under  my  observation  I  was  hopeful  that  the  glycosuria 
would  soon  disappear  under  moderate  dietetic  restriction,  in  accordance  with  opin- 
ions then  prevaihng  and  reports  available  in  the  literature  up  to  that  date.  After  several 
trials  and  speedy  return  of  the  symptoms  it  became  evident  that  there  was  more  than 
a  transient  glycosuria,  though  the  patient's  general  appearance  did  not  indicate  a 
severe  form  of  diabetes. 


ACUTE  INFECTION  AND   DIABETES  1195 

until  December  19,  1915,  when  he  had  a  severe  attack  of  "grippe."  Two 
days  later  pain  in  left  side,  extending  from  the  midclavicular  line  to  the 
posterior  axillary  line  at  the  level  of  the  costal  border;  deep  breathing  or 
coughing  aggravated  the  pain,  which  lasted  about  a  week.  His  "grippe" 
continued  until  January  ist,  and  on  January  6th  he  tried  to  resume  his 
work,  but  found  himself  too  weak  to  continue.  From  the  beginning  of  his 
trouble  he  noticed  great  thirst  and  polyuria.  Sugar  was  discovered  in  urine 
about  January  20th.  Examination  of  urine  three  months  previously,  as 
well  as  earlier  examinations,  did  not  show  sugar.  The  patient's  ordinary 
weight  had  been  145  pounds;  on  admission  it  was  130  p>ounds. 

Physical  examination  showed  no  signs  excepting  enlargement  of  spleen. 
Various  blood  tests,  including  the  estimation  of  the  fragility  of  red  cells, 
proportion  of  skein-cells,  and  morphological  study  of  the  red  cells,  negative. 
Duodenal  contents  showed  the  presence  of  the  pancreatic  ferments  in 
apparently  normal  amounts,  and  a  culture  of  the  duodenal  fluid  showed  the 
presence  of  a  slightly  hemolytic  streptococcus,  but  two  subsequent  cultures 
failed  to  show  this  organism. 

On  admission,  after  two  days  of  a  carbohydrate-free  diet,  somewhat 
rich  in  fats,  the  urine  showed  9.8  grams  of  glucose,  0.42  total  ketones,  13.69 
total  nitrogen  and  0.5  ammonium  nitrogen,  blood-sugar  0.19  p)er  cent. 
He  rapidly  became  sugar-free,  and  two  weeks  after  treatment  the  blood- 
sugar  was  0.09  per  cent.  Subsequently  the  patient  was  able  to  add  carbo- 
hydrate to  his  diet,  in  gradually  increasing  amounts,  without  developing 
glycosuria,  but  under  advice  he  avoided  a  rapid  return  to  full  diet  and  did 
not  resume  his  medical  work  for  a  year.  He  has  had  no  return  of  symptoms 
nor  of  glycosuria. 

Case  IV.  Mild  diabetes  following  vaccinia  and  infection  of  the  arm. 
Readily  controlled  but  relapsing  on  slight  dietary  indiscretions.  T.  H.  D., 
age  seventeen  years,  was  admitted  to  the  hospital  on  September  16,  19 15. 
The  patient  was  reported  as  having  been  perfectly  well  until  he  was  vac- 
cinated on  December  3,  1914.  He  had  a  severe  "take,"  and  was  in  bed  two 
days  with  chills  and  fever.  The  wound  was  infected  and  healed  slowly. 
When  the  boy  returned  home  on  December  23d  from  boarding  school,  his 
mother  noticed  that  he  was  thin  and  had  an  abnormal  thirst  and  craving 
for  food.  The  boy  himself  noticed  three  or  four  days  previously  that  there 
was  increased  frequency  of  urination.  The  urine  was  examined  by  his 
family  doctor  and  found  to  contain  sugar.  On  admission  to  the  hospital 
after  a  light  diet  for  twenty-four  hours,  the  urinary  examination  showed: 
amount  4950  c.c,  glucose  369  grams,  total  nitrogen  14.53  grams,  am- 
monium nitrogen  1.71  grams,  total  ketones  4.9  grams.  Examination  of  the 
pancreatic  secretions  showed  all  the  ferments  present  in  normal  amounts. 


1 196  ACUTE   INFECTION   AND   DIABETES 

Schmidt's  test  showed  normal  pancreatic  secretions  in  the  intestinal  tract. 
There  was  no  abnormal  amount  of  fat  in  the  stools.  On  a  carbohydrate- 
free  diet,  sugar  rapidly  diminished  and  in  five  days  disappeared  entirely. 
A  little  later  he  was  troubled  with  an  abscess  at  the  root  of  one  of  his 
teeth,  which  seemed  to  be  the  occasion  for  the  reappearance  of  sugar,  but 
after  careful  dieting  and  relief  of  the  abscess,  sugar  disappeared  from  the 
urine  in  three  days.  October  ist,  urinary  examination  reads:  amount 
960  c.c,  glucose  negative,  total  nitrogen  8.45  grams,  ammonium  nitrogen 
0.46  grams,  total  ketones  2.55  grams.  The  patient  remained  sugar-free 
with  an  occasional  recurrence  of  sugar  which  was  attributed  to  dietary 
slips.  October  31st  the  urine  report  reads:  amount  2015  c.c,  glucose  nega- 
tive, total  nitrogen  11.46  grams,  ammonium  nitrogen  0.73  gram,  total 
ketones  0.87  gram.  Subsequently,  and  until  the  time  of  his  discharge,  the 
patient  remained  sugar-free.  He  later  had  some  recurrence  of  sugar,  but 
always  as  the  result  of  dietary  indiscretion.  A  year  later  his  father  re- 
ported that  he  had  had  two  remissions,  probably  attributable  to  dietary 
indiscretions,  but  each  of  these  was  readily  controlled  by  more  rigid  dieting. 

Case  V.  Moderately  severe  diabetes  following  pneumonia.  A.  G.  W., 
age  thirty-four  years,  male,  admitted  to  hospital  May  22,  19 16,  on  account 
of  frequent  urination,  polyuria,  and  increased  thirst.  Patient  first  noticed 
these  symptoms  and  also  increased  hunger  about  the  middle  of  February, 
1916,  immediately  following  an  attack  of  pneumonia  from  which  he  was 
not  yet  convalescent.  The  symptoms  began  before  he  left  his  bed  after  the 
pneumonia.  About  March  ist  sugar  was  discovered  in  his  urine.  The 
Wassermann  was  negative.  The  patient  rapidly  became  sugar-free  on  a 
carbohydrate-free  diet,  rather  rich  in  fats,  but  subsequently  showed  a 
tendency  to  recurrences  of  traces  of  sugar  on  a  similar  diet  with  very 
moderate  additions  of  carbohydrate.  At  the  time  of  his  discharge  in  June 
he  was  sugar-free. 

After  discharge  from  the  hospital,  patient  remained  sugar-free  for 
three  months,  when  he  was  persuaded  to  increase  his  diet  considerably, 
and  the  original  symptoms  recurred.  During  the  next  two  years  his  condi- 
tion is  not  recorded.  He  was  readmitted  to  the  hospital  in  July,  1918, 
with  very  much  more  pronounced  evidences  of  diabetes.  On  a  general 
diet,  the  twenty-four  hour  excretion  of  urine  was  3700  c.c,  specific  gravity 
1.038,  glucose  290  grams,  total  nitrogen  17.47  grams,  ammonium  nitrogen 
4.9  grams,  total  ketones  10.75  grams,  plasma  CO2  36  volumes  per  cent, 
and  the  alveolar  air  CO2  18.  On  August  25th  the  urine  report  reads: 
amount  1200  cc,  specific  gravity  1.036,  total  nitrogen  9.72  grams,  glucose 
22.7  grams,  ammonium  nitrogen  3.14  grams,  total  ketones  7.34  grams. 
At  the  time  of  the  patient's  discharge  from  the  hospital  September  5, 


ACUTE  INFECTION  AND  DIABETES 


1 197 


1918,  he  was  in  much  better  condition,  having  been  for  some  days  sugar- 
free  and  free  of  diacetic  acid  reaction. 

URINE. 


■  Diet               Calories 

Quant. 

Sp. 
Gr. 

Glu- 
cose 

Total 

N. 

Ke- 
tones 

Bld. 
CO, 

Am- 
monia 

N. 

5-23-16  House  diet 

3800  c.c. 

1045 

258  g. 

5-24—16] 

Prot.  77.5) 
.Fat   122.5  1452 
C.  H.  10.   J 

710+  c.c. 

1042 

22 

5-25-16 

1165  C.C. 

1023 

3-4 

5-26-16 

1475  C.C. 

1021 

faint 
trace 

5-27-16 

1520  c,c. 

1025 

faint 
trace 

5-28-16 

1430  c.c. 

— 

0 

14-3 

0-4 

0-63 

Readmission 
7-15-18,  full  diet 

3700  c.c. 

1038 

290 

14-47 

10-75 

36% 

4-9 

7-19-18 f Prot.  26.51 

Fat     48.    \  514 
7-20-18 IC  H.    9.    J 

1200  C.C. 

1036 

22-7 

9-72 

7-34 

3.4 

7-30-18,  fasting 

— 

— 

— 

— 

— 

8-  2-18 

2000  C.C. 

0 

In  the  foregoing  cases,  with  the  possible  exception  of  Case  III, 
the  condition  arising  in  the  course  of  or  immediately  following  an 
acute  infection  could  be  properly  designated  as  diabetes,  and  in 
three  there  was  a  considerable  tendency  to  acidosis.  The  statement 
usually  made  by  writers  on  diabetes  that  "the  carbohydrate  toler- 
ance is  reduced  by  febrile  infections"  does  not  suffice,  at  least  in  the 
three  cases  with  tendency  to  acidosis,  to  explain  what  took  place. 
There  were,  in  fact,  all  the  metabolic  phenomena  of  genuine  diabetes, 
including  the  perverted  fat  metabolism  with  the  resulting  acid 
intoxication.  The  thought  readily  suggests  itself  that  there  may 
occur  in  the  course  of  infectious  diseases  the  pancreatic  lesions  that 
occasion  diabetes.  If  this  be  the  case,  explanation  must  be  given 
for  the  fact  that  diabetes  so  rarely  occurs  in  cases  of  "acute  pan- 
creatitis," as  this  disease  is  ordinarily  defined.  In  answer  to  this 
question,  it  may  be  pointed  out  that  diabetes  does  not,  as  a  rule, 
occur  in  various  destructive  lesions  of  the  pancreas,  such  as  car- 
cinoma and  chronic  pancreatitis  of  biliary  origin,  and  the  acute 
pancreatitis  commonly  recognized  clinically  probably  belongs  to  the 
same  group  of  conditions,  and  is  no  doubt  the  result  of  irritations 
or  infections  ascending  the  pancreatic  ducts  from  the  duodenum. 


iipS  ACUTE  INFECTION  AND  DIABETES 

whereas  the  lesions  of  the  pancreas  that  occasion  diabetes  more 
likely  have  a  hematogenous  origin.  Hematogenous  infection  of  the 
pancreas,  like  involvement  of  other  glands,  is  undoubtedly  common 
in  various  infectious  diseases;  the  occurrence  of  diabetes  as  a  sequel 
of  infection  is,  therefore,  not  improbable.  As  a  matter  of  fact  I  have 
observed  one  fatal  case  of  acute  pancreatitis  with  rapidly  developed 
diabetes  and  death  in  coma  (to  be  reported  later)  and  another  case 
of  severe  diabetes  originating  in  an  acute  pancreatitis  of  unknown 
etiology.  It  does  not  seem  to  me  improbable  in  such  marked  in- 
stances as  Case  I,  that  the  infection  caused  an  acute  lesion  of  the 
pancreas  capable  of  producing  the  phenomena  of  diabetes,  or  that 
in  other  cases,  and  perhaps  much  more  frequently  than  now  appears 
probable  from  available  evidence,  pancreatic  lesions  initiated  dur- 
ing infections  eventually  become  sufficiently  extensive  to  occasion 
diabetes. 

III.  Opinions  regarding  the  effect  of  infectious  diseases  on  an 
existing  diabetes  seem  to  have  undergone  considerable  alteration. 
Older  writers  quite  uniformly  refer  to  the  ameliorating  influence 
of  infections  in  a  certain  proportion  of  cases,  while  the  attitude  of 
contemporary  authorities  is  to  regard  infections  as  uniformly 
unfavorable.  Naunyn  (34)  says  that  "The  reduction  of  glycosuria 
up)on  the  incidence  of  acute  febrile  infections  is  simply  astonishing," 
and  elsewhere  (35)  he  discusses  the  .improvement  in  the  diabetic 
condition  during  or  following  typhoid  fever,  pneumonia,  relapsing 
fever,  and  other  infections.  While  his  statement  gives  the  impression 
that  this  favorable  eff'ect  of  infections  is  usual,  he  mentions  cases 
and  published  records  that  indicate  the  reverse,  and  in  particular, 
refers  to  the  fact  that  sometimes  diabetic  individuals  temp>orariIy 
sugar-free  exhibit  a  return  of  glycosuria  after  the  onset  of  an  in- 
fection, giving  the  appearance  of  diabetes  resulting  from  the  infec- 
tion. He  makes  special  mention  of  the  fact  that  glycosuria  increases 
with  the  development  of  boils,  carbuncles,  or  gangrene  and  greatly 
diminishes,  or  disappears,  upon  opening  or  drainage  of  the  purulent 
collections  or  amputation  of  the  gangrenous  extremity.  Von  Noorden 
(36)  says:  "I  have  already  had  occasion  to  note  the  fact  that 
in  many  cases  of  diabetes  the  urine  becomes  less  saccharine  or 
entirely  sugar-free  during  the  intercurrence  of  an  acute  pyretic 
infectious  disease.  This  is  an  old  experience.  Typhoid  fever  and 


ACUTE  INFECTION  AND  DIABETES  1199 

relapsing  fever  are  most  commonly  known  as  glycosuria-Iessening; 
I  have  observed  the  same  result  in  fibrinous  pneumonia  and  in- 
fluenza." On  the  other  hand,  like  Naunyn,  he  believes  that  certain 
instances  of  apparent  onset  of  diabetes  during  or  after  infections 
are  really  cases  in  which  a  latent  (or  temporarily  aglycosuric) 
diabetes  has  been  revived  by  the  infectious  disease.  Lepine  favors 
the  view  that  infections  are  prone  to  aggravate  diabetes,  and,  in 
particular,  emphasizes  the  unfavorable  eff"ect  of  influenza.  However, 
he  quotes  the  case  of  Glaessner,  (37)  in  which  a  severe  diabetes 
with  acidosis  was  apparently  cured  by  an  attack  of  pneumonia. 
Kleen  (38)  also  refers  to  the  favorable  eff"ect  of  infections  in  some 
cases,  and  contrary  to  Lepine,  mentions  distinct  improvement  after 
influenza.  My  own  experience  coincides  entirely  with  that  of  Joslin: 
"Almost  without  exception  intercurrent  infections  have  increased 
the  severity  of  an  active  diabetes,  and  in  a  large  proportion  of  cases 
have  been  the  immediate  forerunners  of  coma."  Several  of  my  cases, 
in  which  the  disease  was  either  quiescent  or  clinically  cured,  at 
once  relapsed  upon  the  occurrence  of  an  infection.  This  will  be  noted 
in  the  later  history  of  one  of  the  cases  cited  above  as  instances  of 
diabetes  originating  from  infection  (Case  I),  and  will  be  further 
illustrated  in  the  following  group.  A  very  instructive  instance  show- 
ing the  unfavorable  influence  of  infections  was  that  of  a  medical 
colleague  who  was  the  victim  of  the  disease.  During  several  years 
he  had  from  time  to  time  recurring  attacks  of  acute  sinus  infection, 
after  each  of  which  there  was  a  sharp  increase  in  his  diabetic  symp- 
toms and  distinct  evidences  of  acidosis.  His  final  and  fatal  attack 
ending  in  coma  was  precipitated  by  the  same  cause. 

The  following  cases  illustrate  the  tendency  of  diabetes  to  relapse 
upon  the  occurrence  of  acute  infections.  In  these  cases  there  was 
less  evidence  that  the  original  onset  of  the  condition  was  attributable 
to  infection,  though  the  probability  was  considerable  in  Case  VI. 

Case  VI.  Diabetes  probably  following  antrum  infection.  Recurrence 
and  rapidly  developed  coma  following  facial  erysip>clas.  F.  M.,  age  fifty 
years,  negro,  was  admitted  December  22,  1916,  on  account  of  an  acute 
febrile  illness  which  began  two  days  previously.  There  was  severe  cough 
and  some  expectoration,  considerable  coryza,  mucous  nasal  discharge, 
pain  in  the  right  side  provoked  by  deep  breathing  and  coughing.  The  patient 
also  had  severe  frontal  headache  and  tenderness  over  the  right  antrum. 


i;200  ACUTE  INFECTION  AND  DIABETES 

Subsequently  there  was  marked  evidence  of  sinus  trouble.  On  December 
29th  the  left  antrum  was  opened  and  found  full  of  foul-smelling  pus. 
There  was  also  opacity  of  the  left  frontal  sinus  which  required  subsequent 
flushing. 

The  patient's  previous  medical  history  was  of  no  definite  significance 
in  connection  with  the  diabetic  condition  subsequently  discovered.  He 
had  had  some  of  the  diseases  of  childhood  and  pneumonia  on  the  right  side 
four  years  previously;  also  malarial  fever  twenty-five  years  previously. 
There  was  no  history  of  venereal  infection.  He  was  a  married  man  with 
five  healthy  children  living;  was  a  chauffeur  and,  consequently,  was  con- 
siderably exposed  to  the  weather.  Family  history  negative. 

The  first  examination  of  his  urine  after  admission  showed  considerable 
sugar,  acetone,  and  diacetic  acid.  A  twenty-four  hour  collection,  after  a 
carbohydrate-free  diet  of  about  2000  calories,  was  750  c.c,  specific  gravity 
1.032,  glucose  8.25  grams;  a  second  twenty-four  hour  collection  was  900 
c.c.  and  contained  14.5  grams  of  sugar.  On  both  occasions  a  strong  acetone 
reaction  and  a  marked  ferric  chloride  reaction  were  obtained.  Complete 
chemical  studies  were  not  made.  On  a  carbohydrate-free  diet,  the  amount 
of  sugar  diminished  to  faint  traces,  and  after  four  days  of  green  diet,  the 
sugar  disappeared  entirely. 

Subsequent  inquiries  developed  the  fact  that  there  had  been  no  sugar 
in  the  patient's  urine  on  any  occasion  previous  to  his  acute  illness.  A  number 
of  examinations  had  been  made  on  different  occasions. 

Readmission.  Patient  was  readmitted  to  the  hospital  March  5,  19 19. 
On  March  2d  an  operation  for  the  drainage  of  one  of  the  accessory  sinuses 
of  the  nose  was  done  at  another  hospital,  and  the  patient  allowed  to  return 
to  his  home  a  few  days  later.  He  was  admitted  to  the  University  Hospital 
on  the  above  date  with  a  well-developed  facial  erysipelas  and  marked 
fever,  ranging  from  104°  to  105°.  He  stated  that  during  the  two  years 
since  his  former  admission  to  this  hospital  he  had  become  careless  regarding 
his  diet  and  intermittently  had  suffered  from  polyuria,  especially  recently. 

On  admission,  the  urine  examination  (morning  specimen)  was  reported 
as  follows:  specific  gravity  1.022,  acid,  no  albumin,  no  sugar,  no  casts. 

As  a  precaution  against  possible  acidosis  the  patient  was  put  on  a  diet 
containing  considerable  carbohydrate  in  the  form  of  oatmeal  and  other 
cereals  and  one-half  ounce  of  whisky  was  given  at  third-hour  intervals. 
March  i6th:  Twenty-four  hours  collection  of  urine  showed  neither  sugar 
nor  ketone  bodies.  March  17th:  Blood  urea  N,  15  milligrams,  plasma  CO2 
46  volumes  per  cent,  blood-sugar  0.18  per  cent.  March  i8th:  Urine,  amount 
1040  c.c,  specific  gravity  1.030,  total  nitrogen  8.82  grams,  glucose  34.3 
grams.  Ammonium  nitrogen  1.02  grams,  total  ketones  5.8  grams,  a  trace 


ACUTE  INFECTION  AND  DIABETES  1201 

of  albumin,  and  many  granular  casts.  March  19th:  Blood  urea  N,  30 
milligrams,  blood-sugar  0.37  per  cent,  blood  CO2  22  volumes  per  cent. 

On  March  i8th  the  patient  grew  more  and  more  drowsy  and  died  in 
coma  on  March  19th. 

Case  VII.  Mild  diabetes  recurring  acutely  during  an  attack  of  influenza. 
A.  H.,  age  sixteen  years,  admitted  to  the  hospital  Decemt)er  16,  1917.  Had 
first  experienced  frequency  of  urination  and  marked  thirst  about  2^  months 
previously.  Soon  he  began  to  lose  weight  and  in  all  lost  14  pounds  up  to  the 
time  of  admission.  Appetite  was  enormous,  but  he  was  growing  steadily 
weaker.  Patient  weighed  on  September  i6th  123  pounds,  and  on  December 
17th,  103. 

The  patient's  tonsils  and  adenoids  had  been  removed  four  years  before, 
but  he  had  suffered  from  an  attack  of  ulcerative  sore  throat  five  months 
before  the  onset  of  the  present  symptoms,  and  had  practically  not  been  well 
from  then  up  to  the  time  the  present  illness  was  observed.  In  November, 
191 7,  the  patient  had  been  in  another  hospital,  where  the  following  analyses 
of  the  urine  were  reported:  November  15th,  sugar  31.25  grams  per  hundred 
C.C.;  19th,  sugar  3.12  grams  per  hundred  c.c;  23d,  sugar  0.25  gram  per 
hundred  c.c;  26th,  negative. 

Between  this  date  and  admission  to  the  University  Hospital  the  gly- 
cosuria had  reappeared. 

On  a  carbohydrate-free  diet  he  was  quickly  rendered  sugar-free,  and 
remained  so  during  the  two  weeks  that  he  was  in  the  hospital,  except  on 
one  day,  when  he  excreted  7.2  grams  of  glucose,  probably  on  account  of  a 
little  intake  of  fruit. 

From  the  date  of  discharge  from  the  hospital,  December  20,  1917, 
until  January  19,  19 19,  the  patient  remained  sugar- free  with  two  excep- 
tions, when  during  one  day  from  excessive  intake  of  fruit,  traces  of  sugar 
were  found.  His  diet  ranged  from  50  to  70  grams  of  protein,  100  to  120  grams 
of  fat  and  from  40  to  80  grams  of  carbohydrate.  He  was  engaged  in  light 
office  work. 

During  December,  1918,  he  had  a  mild  attack  of  influenza  and  im- 
mediately thereafter  he  experienced  symptoms,  and  sugar  reappeared  in 
the  urine  in  considerable  quantity.  He  was  at  once  put  on  a  carbohydrate- 
free  diet  with  considerable  reduction  in  both  fats  and  protein  and  became 
sugar-free  in  a  few  days.  After  two  weeks  rest  from  work,  he  was  prac- 
tically in  the  same  condition  as  before  the  attack  of  influenza,  and  since 
then  has  gradually  resumed  a  full  diet  low  in  fats,  but  with  considerable 
addition  of  carbohydrate. 

Case  VIII.  Severe  (or  prolonged)  diabetes;  apparent  recovery  under 
treatment;  rapid  recurrence  and  death  in  coma  during  an  attack  of  in- 


1202 


ACUTE  INFECTION  AND  DIABETES 


fluenza.  F.  H.  M.,  age  thirty  years,  male,  admitted  to  hospital  March  i, 
1916,  on  account  of  severe  diabetes.  His  physician  stated  that  the  patient's 
illness  began  about  four  years  before  without  apparent  cause.  The  patient 
first  noticed  thirst  and  marked  fatigability;  later  he  complained  of 
gastrointestinal  disorders  and  nervous  depression.  Sugar  had  been  dis- 
covered almost  at  the  beginning  of  the  illness,  and  he  was  never  sugar-free, 
though  some  attempts  at  strict  dieting  had  been  made.  The  patient  was 
extremely  emaciated,  temples  sunken,  skin  pallid,  and  a  marked  acetone 
odor  was  noticed  in  the  room  where  he  was  sitting.  No  special  physical 
signs.  On  a  light  diet,  not  restricted  as  to  carbohydrates,  the  output  of 
urine  was  2850  c.c,  specific  gravity  1.039,  glucose  150  grams  and  acetone 
and  diacetic  acid  +  + .  Subsequently  after  three  days'  fasting  he  became 
sugar-free  and  remained  so  with  rare  exceptions,  when  traces  of  sugar 
reappeared.  The  diet  was  rather  too  high  in  fats,  and,  though  sugar-free, 
the  urine  contained  diacetic  acid  till  shortly  before  the  patient's  discharge 
from  the  hospital  (April  30,  19 16). 


Amount 

Sp.  Gr. 

Glucose 

Total  N. 

Ammonia 

N. 

Ketones 

3-  9-16 

1240  c.c. 

1040 

30-3  gms. 

11-1  gms. 

2-77  gms. 

8-89 

3-30-16 

1570  c.c. 

1015 

negative 

9-8  gm. 

0-35  gm. 

0-812 

Weight  on  admission  was  10 1  pounds,  and  at  the  time  of  discharge, 
98  pounds.  After  discharge  from  the  hospital,  increasing  amounts  of  carbo- 
hydrates were  added  to  his  diet.  Weight  and  strength  increased  steadily. 
January  i,  191 7,  he  weighed  ii3/^  pounds;  subsequently  remained  sta- 
tionary at  about  this  point.  Sugar  never  reappeared  in  the  urine  until  his 
fatal  illness. 

On  November  27,  19 18,  patient  had  symptoms  of  a  mild  attack  of 
influenza,  and  was  put  to  bed  at  once.  He  improved  so  much  that  his 
physician  did  not  think  it  necessary  to  see  him  every  day.  He  last  visited 
him  December  i,  191 8,  and  found  his  patient  in  good  condition.  On  De- 
cember 2d  the  patient  went  into  sudden  coma,  and  death  occurred  during 
the  night,  December  3d. 

Case  IX.  Mild,  but  prolonged,  diabetes;  rapid  recurrence  and  death 
in  coma  during  an  attack  of  croupous  pneumonia.  Mrs.  L.  J.  S.,  age  sixty- 
six  years,  consulted  me  on  March  12,  19 18,  on  account  of  diabetes,  which 
was  recognized  five  years  previously.  In  the  beginning  of  her  illness  there 
was  marked  thirst  and  frequent  urination.  Under  strict  diet  she  had  been 
relieved  of  these  symptoms  and  the  glycosuria,  but  had  recurrences  of 
sugar  with  any  attempt  at  increasing  her  diet.  At  her  first  visit  a  sample  of 


ACUTE  INFECTION  AND  DIABETES  1203 

urine  showed  a  small  quantity  of  sugar,  but  the  twenty-four  hour  excretion 
was  not  determined.  With  restriction  of  her  diet,  the  sugar  promptly 
disappeared,  and  during  the  next  six  months  was  constantly  absent  in 
the  twenty-four-hour  collections.  A  slight  return  was  noted  on  one  occasion 
at  this  time,  but  thereafter  she  remained  sugar-free  for  another  six  months. 
On  February  15,  19 19,  after  having  been  free  of  sugar  for  twelve  months, 
she  was  seized  with  a  severe  attack  of  croupous  pneumonia.  Her  physician 
found  a  large  amount  of  sugar  on  the  same  day  and  when  I  saw  her,  twenty- 
four  hours  later,  she  was  in  a  stuporous  state  with  apparent  diabetic 
acidosis.  The  urine  contained  2.5  per  cent  sugar  and  showed  a  marked 
ferric  chloride  reaction  for  diacetic  acid.  She  died  a  few  hours  later  with 
increasing  pulmonary  engorgement  and  with  pronounced  coma. 

Conclusions.  The  cases  of  diabetes  here  reported  illustrate  the 
occasional  onset  of  this  disease  during  or  immediately  following 
acute  infections,  and  the  marked  tendency  of  infectious  diseases  to 
cause  recurrence  of  diabetic  conditions  after  the  arrest  or  apparent 
cure  of  the  disease.  The  recurrence  of  diabetic  phenomena  in  two  of 
the  cases  (Case  I  and  Case  VIII)  after  apparent  cure  of  four  and 
two  years'  duration  respectively,  immediately  after  the  onset  of 
acute  infections,  indicates  the  difficulty  in  determining  whether 
or  not  the  arrested  disease  is  actually  cured.  The  greater  intensity 
of  the  disease  when  recurring  after  primary  arrest  (Case  V,  and 
less  clearly  Case  VI)  indicates  the  probability  that  many  of  the 
instances  reported  in  literature  as  transient  glycosuria  in  the  course 
of  infection  might  have  later  recurred  as  genuine  diabetes,  when  the 
original  infectious  origin  would  not  have  been  recognizable.  Un- 
doubtedly infection  must  be  regarded  as  a  probable  cause  of  the 
pancreatic  lesions  that  occasion  diagnosis,  and  for  which  at  present 
no  established  etiology  is  recognized.  The  evidence  of  such  cases  as 
are  here  reported  is  of  course  regarded  merely  as  suggestive. 

BIBLIOGRAPHY 

1.  Festscbr.  des  stddtiscb.  Krankenbaus,  Frankfort,  1896. 

2.  Biocbem.  Zeitscbr.,  1906,  299. 

3.  Deutscbes  Arcb.J.  klin.  Med.,  1907-08,  XCII,  217. 

4.  Ibid.,  1911,  CIV,  437. 

5.  Quoted  by  Naunyn,  "Der  Diabetes  Melitus,"  1898,  113. 

6.  "Twentieth  Century  Practice,"  II,  6$. 


1204  ACUTE  INFECTION  AND  DIABETES 

7.  "Treatment  of  Diabetes  Mellitus,"  2d  Ed.,  62. 

8.  "Diabetes  Mellitus,"  P.  Blakiston's  Sons  &  Co.,  Philadelphia,  1900. 

9.  For  literature,  Kleen  refers  to  Jacobsohn,  "Diabetes  Melitus,"  Dis- 

sertation, Rostock,  1896. 

10.  Union  mid.,  1872,  XIV. 

1 1.  Bull.  Acad,  de  mM.,  1881. 

12.  Gaz.  Hebd.,  1882,  801. 

13.  Kiilz,  "Klin.  Erfahrungen,"  1899,  248. 

14.  "Le  Diab^te  Sucr^,"  Paris,  1909. 

15.  "Trait6  du  Paludism." 

16.  Gaz.  Hebd.,  1882. 

17.  Quoted  by  Buhl,  Zeitscbr.  /.  Rationelle  Heilkunde,  1857. 

18.  Arch.  J.  Heilkunde,  1867,  VIII,  331. 

19.  Gaz.  d.  H6p.,  1866,  410. 

20.  Bull,  de  la  Suisse  Rom. 

21.  J.  Exper.  M.,  1889,  IV,  137. 

22.  Boston  M.  &■  S.  J.,  1899,  20. 

23.  Lancet,  Lond.,  March  2,  1912. 

24.  "La  Diab^te  Sucre,"  401. 

25.  Handbucb  d.  Kinderb.,  1883,  XIX,  216. 

26.  Arcb.j.  Kinderb.,  1890,  XI,  81. 

27.  Loc.  cit. 

28.  Deutsche  Med.  Ztg.,  1900,  121 1. 

29.  Deutsche  med.  Wcbnscbr.,  1906,  25. 

30.  Miincben  med.  Wcbnscbr.,  1903,  26. 

31.  Loc.  cit. 

32.  Ztscbr.  f.  klin.  Med.,  XX,  272. 

33.  Loc.  cit. 

34.  Loc.  cit.,  page  141. 

35.  Loc.  cit.,  pages  141,  142,  330. 

36.  Loc.  cit.,  p.  85. 

37.  Wien.  klin.  Wcbnscbr.,  1906,  No.  29. 

38.  Loc.  cit. 


THE  SIGNIFICANCE  OF  RICKETTSIA  IN  RELATION 

TO  DISEASE 

By  Richard  P.  Strong,  M.D. 

IN  19 1 6  Rocha-Lima  called  attention  to  the  presence  of  very 
minute  bodies  which  were  found  in  lice  which  had  fed  upon 
patients  suffering  with  typhus  fever.  These  bodies  were  present 
not  only  in  the  contents  of  the  alimentary  canal,  but  especially  in 
the  epithehal  cells  of  the  alimentary  tract  of  these  insects.  He 
regarded  them  as  very  minute  micro-organisms.  They  were  ellip>- 
tical,  oval,  often  found  in  pairs,  and  bipolar  in  appearance.  The 
smaller  forms  measured  from  about  .3  to  .4  micron,  and  the  larger 
ones,  sometimes  biscuit-shaped,  from  .4  to  .9  micron.  They  were  best 
demonstrated  by  staining  in  Giemsa's  solution.  These  organisms 
were  not  at  first  found  in  lice  which  had  not  fed  upon  cases  of 
typhus  fever.  The  lice  were  said  to  become  parasitized  only  after 
ingesting  infected  blood.  Rocha-Lima  pointed  out  that  while  these 
bodies  slightly  resembled  bacteria  in  their  morphology,  they  were 
in  other  respects  more  Hke  the  Cblamydozoa  strongyloplasmata. 
He,  therefore,  proposed  for  them  the  name  of  Rickettsia  prowazeki 
(n.g.  n.sp.),  evidently  choosing  this  name  in  memory  of  Ricketts 
and  Prowazek,  both  of  whom  succumbed  to  typhus  fever,  which 
they  contracted  while  pursuing  their  independent  investigations 
upon  this  disease.  Subsequently,  organisms  having  a  similar  ap- 
pearance were  found  by  other  observers,  and  also  by  Rocha-Lima, 
in  lice  which  had  fed  upon  healthy  individuals  or  on  those  suffering 
with  various  other  diseases.  For  this  second  form  Rocha-Lima  pro- 
posed the  name  of  Rickettsia  pediculi.  He  believes  that  Rickettsia 
pediculi  differs  from  Rickettsia  prowazeki  in  that  the  former  is  found 
normally  only  in  the  lumen  of  the  ahmentary  canal  of  the  louse, 
and  does  not  multiply  in  the  cells  of  the  insect's  alimentary  tract, 
or  does  so  only  exceptionally. 

It  is  of  importance  in  considering  the  study  of  the  Rickettsia 
to  recall  that  the  terms  Chlamydozoa  (Prowazek)  (i),  Strongy- 

1205 


i2o6         THE  SIGNIFICANCE   OF   RICKETTSIA 

loplasmata  (Lipschutz)  (2)  were  proposed  to  include  a  group  of 
very  minute  pathogenic  organisms  or  viruses  which  exhibited  certain 
common  properties,  while  exercising  specific  peculiarities  in  each 
case.  These  viruses  are  believed  during  at  least  one  stage  of  their 
development  (that  of  the  "elementary  corpuscles")  to  pass  through 
bacterial  filters  without  losing  their  virulence.  Within  the  cells  of 
the  host  the  elementary  corpuscles  are  believed  to  grow  into  larger 
"initial  bodies.** 

The  chief  characteristics  of  the  Chlamydozoa  (3)  were  said  to 
be  first,  their  minute  size,  smaller  than  any  bacteria  hitherto  known, 
enabling  them  to  pass  the  ordinary  bacterial  filters  during  one  stage 
of  their  development;  second,  that  they  develop  within  cells,  in  the 
cytoplasm  or  nucleus,  and  produce  characteristic  reaction  products 
and  enclosures  of  the  cell;  third,  that  they  pass  through  a  series  of 
developmental  stages,  and  are  specially  characterized  by  their  mode 
of  division,  which  is  not  a  simple  process  of  splitting,  as  in  bacteria, 
but  is  eff'ected  with  formation  of  a  dumb-bell-shaped  figure,  as  in 
the  division  of  a  centriole.  Two  dots  are  seen,  connected  by  a  fine 
line  like  a  centrodesmose,  which  becomes  drawn  out  until  it  snaps 
across  the  middle,  and  its  two  halves  are  then  retracted  into  the 
body.  In  appearance  the  Chlamydozoa  seem  to  consist  primarily 
of  merely  a  grain  of  chromatin  without  cytoplasm  and  without  a 
membrane  of  any  kind.  Hence  they  appear  to  represent  the  simplest 
form  of  living  body.  The  Chlamydozoa  have  not  yet  been  success- 
fully cultivated,  but  infections  can  be  produced  with  pure  colloid- 
filtrates  free  from  bacteria,  but  containing  the  minute  bodies  them- 
selves. They  are  characteristically  parasites  of  epiblastic  cells  and 
tissues.  The  viruses  of  trachoma,  vaccinia,  scarlet  fever,  hydro- 
phobia, molluscum-contagiosum,  and  more  recently  of  typhus  fever, 
have  been  referred  to  the  Chlamydozoa. 

Previous  to  Rocha-Lima's  observations,  several  investigators 
besides  Ricketts  had  published  articles  describing  micro-organisms 
observed  in  lice  which  had  fed  upon  typhus  fever  patients,  and 
Ricketts  also  described  a  somewhat  similar  organism  in  connection 
with  Rocky  Mountain  fever.  The  results  of  these  investigations  have 
been  summarized  in  the  following  table: 


THE   SIGNIFICANCE   OF   RICKETTSIA         1207 


TABLE  SHOWING  THE  PRESENCE  OF  RICKETTSIA  BODIES. 


YEAR 

INVESTIGATOR 

RICKETTSIA  BODIES  OR  ORGANISMS 
resembling  THEM  FOUND  IN 

1909 

RiCKETTS 

Blood  of  guinea  pigs  and  monkeys  infected 
with  blood  from  Rocky  Mountain  spotted 
fever  cases.  Also  seen  in  blood  of  man,  and 
in  female  tick  {Dermacentor  occidentalis) 
and  in  eggs  of  these  ticks  fed  upon  in- 
fected guinea  pigs. 

I9IO 

RlCKETTS  AND  WlU)ER 

Studies  in  Mexico.  Blood  of  typhus  patients. 
Also  in  dejecta  and  various  organs  of  lice 
fed  on  typhus  patients.  Occasionally 
found  in  feces  ancl  intestinal  contents  of 
normal  lice. 

I9IO 

Gavin  and  Girard 

Blood  of  patients  in  Mexico.  Significance  of 
bodies  obscure. 

1913 

Prowazek 

Blood  of  51  typhus  cases  in  Belgrade.  In 
examination  of  sections  of  organs  of 
typhus  cases,  trachoma-like  bodies  ob- 
served in  endothelial  cells  of  heart,  lung, 
liver,  kidney.  One  infected  louse  con- 
tained coccoid  bodies  and  diplococcus 
forms. 

I9I4 

Seargent,  Foley  and  Vialette 

Lice  living  onlv  on  the  sick,  never  in  lice 
living  on  healthy  people,  or  recurrent  fever 
>atients,  in  Algeria.  Found  especially  in 
jloody  fluid  of  digestive  tract  of  the  lice. 
A  number  of  such  lice  fed  on  healthy  in- 
dividuals and  prop>ortion  of  microbes  seen 
became  much  larger.  Could  not  cultivate 
micro-organism  on  artificial   media. 

I9I4 

NicoLLE,  Blanc,  and  Conseil 

Tunis,  in  5  per  cent  of  lice  collected  in  dis- 
tricts free  from  typhus  for  two  years. 
Lice  fed  on  typhus  cases  are  constantly 
infectious  on  ninth  and  tenth  day,  not 
before  the  eighth.  Organisms  not  detected 
in  blood  and  organs  of  guinea  pigs  in- 
fected with  typhus. 

I9I5 

Proescher 

Blood  smears  from  nine  typhus  cases  showed 
bodies  in  endothelial  cells  from  blood  ves- 
sels. Very  few  seen  in  plasma  and  in  poly- 
nuclear  leucocytes.  These  bodies  not 
found  in  normal  blood  or  in  blood  from 
cases  of  measles,  mumps,  scarlet  fever, 
cholera,  relapsing  fever. 

I916 

Dorendorf 

Blood  of  typhus  fever  cases  in  Serbia  ex- 
amined, and  organisms  described  by 
Prowazek  discovered  in  all  cases  examined 
during  febrile  stage.  Found  in  plasma  and 
in  polymorphonuclear  and  mononuclear 
leucocytes. 

I916 

Stemple 

Among  the  enigmatic  parasites  in  the  in- 
testinal epithelium  in  dissected  lice  col- 
lected from  sick  people. 

I208 


THE   SIGNIFICANCE   OF   RICKETTSIA 


TABLE  SHOWING  THE  PRESENCE  OF   RICKETTISA  BODIES— Continued. 


YEAR 

INVESTIGATOR 

RICKETTSIA  BODIES  OR  ORGANISMS 
RESEMBLING  THEM  FOUND  IN 

I916 

LiPSCHxrrz 

Polymorphonuclear  leucocytes  in  blood  from 
typhus  cases;  2^  examined,  18  were  posi- 
tive. These  bodies  not  found  in  control 
preparations  from  typhoid  fever  and  vari- 
ola cases,  or  in  normal  blood  preparations. 

1916 

CSERNEL 

1  Typhus  blood. 

I916 

ZOI.I.F.NKOPF 

In  describing  a  new  disease  resembling  in- 
termittent    fever     (probably     Wolhynian 
fever)    found   changes   in   red   cells.    Not 
found  in  preparations  taken  after  the  fever. 

I916 

RoCHA-LlMA  AND  PrOWAZEK 

Investigations   at    Prison    Camp,    Kottbus, 
95  per  cent  of  lice  taken  from  sick  people 
were  infected  by  parasitic  micro-organism. 
Organisms  found  in  contents  of  alimen- 
tary canal,  and  especially  in  epithelial  cells 
of  alimentary   tract.    Not   found   in   lice 
living  on  healthy  subjects.  Non-infected 
lice  placed  on  sick  patients  became  in- 
fected. This  parasite  found  in  man  only 
in  leucocytes. 

I916 

RoCHA-LlMA 

In  1914  (December)  in  streak  preparations 
made  from  lice  fed  on  typhus  cases,  found 
large  numbers  of  bodies.  Recognized  by 
Prowazek  as  the  same  as  seen  by  him  in 
19 1 3  in  preparation  from  infected  louse. 

In    examination    of   sections    of   lice    from 
typhus  cases,  and  of  normal  lice,  bodies 
found  in  large  numbers  in  cells  of  ali- 
mentary canal  and  in  salivary  glands  of 
infected  lice;  not  in  normal  lice;  17  out  of 
18  lice  from  a  sick  patient  were  infected. 
Rickettsia  appeared  in  cells  of  intestine  of 
lice  on  fourth  or  fifth  day.  Louse  fed  on 
typhus   patient    showed    Rickettsia    four 
days  afterwards. 

I917 

MtWK^AND  RoCHA-LiMA 

Found  diplobacillus  in   blood  of  Wolhynian 
fever  cases,  but  also  found  same  in  blood 
from  patients  with  other  diseases,  or  even 
from  nealthy  ones. 

Munk  made  70  experiments  on  patients  diag- 
nosed as  Wolhynian  fever  cases — 51  posi- 
tive for  R.  pediculi,  1 1  negative,  6  doubtful. 
Among  negatives  were  some  typical  cases. 

Among  33  control  tests,  26  were  negative 
and  6  infected  same  as  lice  from  Wolhynian 
fever  cases.  These  6  cases  upon  which  the 
lice  were  fed,  which  proved  jwsitive  for 
Rickettsia,    were    3    malaria,    i    bladder 
disease,    i    bronchitis,    i    inguinal   hernia. 
One  normal  gave  rise  to  strongly  infected 
lice. 

Rocha-Lima  and  Korbsch  attempted  prop- 
agation   of    Wolhynian    fever    with    lice, 
but  not  successfully,   although  lice  were 
strongly  infected. 

THE   SIGNIFICANCE   OF   RICKETTSIA  1209 

TABLE  SHOWING  THE  PRESENCE  OF   RICKETTSIA   BODI ES-Coruinuerf. 


YEAR 

INVESTIGATOR 

RICKETTSIA  BODIES  OR  ORGANISMS 
RESEMBLING  THEM  FOUND  IN 

I916 

NOI.I.F.R 

Lice  from  pigs  transferred  from  infected 
guinea  pigs  to  pig  blood. 

1917 

TOEPFER  AND  SCHUESSLER 

In  400  lice  which  had  fed  on  35  patients, 
bacteria-like  organisms  were  found  in  the 
infected  lice.  Organisms  found  constantly 
in  intestinal  canal  and  of  lice  removed 
from  typhus  patients,  and  often  in  ceils  of 
alinientarv  tract.  Control  lice  fed  on  other 
individuals  than  those  suffering  with 
typhus  fever  remained  free.  Organisms 
found  only  in  lice  fed  on  blood  of  typhus 
patients  during  febrile  (not  post-febrile) 
period. 

I916 

TOEPFER 

Blood  of  Wolhynian  fever.  Also  in  lice  from 
typhus  fever  patients. 

Lice  from  typical  Wolhynian  fever  con- 
tained bodies  in  alimentary  tract  similar 
to  typhus  fever  organism.  Bodies  both  free 
and   inside  the  cells. 

I916 

TOEPFER 

Examined  smears  and  sections  of  500  lice. 
Confirmed  his  former  observations  regard- 
ing organism  in  infected  lice. 

Same  parasite  found  in  lice  from  head  of 
jatients  and   artificially   infected   normal 
ice  of  this  species  by  placing  them  upon 
the  sick.  Smears  from  lice  fed  on  typhus 
blood  contained  organism. 

Described  intracellular  diplobacilli  in  tis- 
sues of  typhus  patients. 

I916 

Hanser 

Confirms  Toepfer's  discovery  of  forms  in 
intestinal  cells  of  lice  fed  on  typhus 
patients. 

I917 

ToEPFER 

In  article  on  war  nephritis  describes  similar 
organisms  to  those  seen  in  lice  fed  on  CMses 
of  typhus  or  Wolhynian  fever.  Found 
similar  organisms  in  three  diseases,  i.e., 
spotted  fever,  Wolhynian  fever,  and 
nephritis. 

I9I7 

Orro  AND  Dietrich 

In  lice  placed  on  patients.  Infection  not 
hereditary.  They  infected  lice  with  Rick- 
ettsia by  feeding  them  on  a  case  of  typhus 
fever  without  tne  exanthem. 

I916 

WOLBACH 

Baciilary  bodies  arc  present  in  large  numbers 
in  endothelial  cells  of  guinea  pigs  infected 
with  the  virus  of  Rocky  Mountain  spotted 
fever  through  the  bites  of  infected  ticks. 

I916 

WOLBACH 

Organism  found  in  experimentally  infected 
ticks,  similar  to  those  previously  seen  in 
tissues  of  monkeys  and  guinea  pigs,  but 
never  in  non-infected  ticks.  Parasites 
most  abundant  in  striped  muscle,  Malpig- 
hian  tubes,  salivary  glands,  and  ducts  and 
brain  ganglia.  Numerous  in  muscle  fibers 
of  uterus  and  vagina,  and  seen  in  the  sper- 
matozoa. Also  in  lesions  of  blood  vesseb 
in  fatal  human  cases  of  Rocky  Mountain 
spotted  fever. 

I2I0         THE   SIGNIFICANCE   OF   RICKETTSIA 


TABLE  SHOWING  THE  PRESENCE  OF   RICKETTISA  BODIES-Continued. 


YEAR 

INVESTIGATOR 

RICKETTSIA  BODIES  OR  ORGANISMS 
RESEMBLING  THEM  FOUND  IN 

I912 

DOEHLE 

Discovered  intra-leucocytal  bodies  in  scar- 
latina cases. 

Preisich 

Recognized  same  bodies  in  other  diseases. 

1917 

Lopez 

Blood  of  typhus  fever,  found  same  intra- 
leucocytal  bodies,  in  77  cases  out  of  90. 
Blood  must  be  taken  from  well-marked 
cases  and  at  the  height  of  the  fever,  to 
contain  these  bodies. 

I9I7 

Schmidt 

Organisms  found  in  3  cases  only,  out  of  many 
cases  of  five-day  lever  examined. 

I917 

JUNGMANN  AND  KuCZYNSKI 

Blood  of  typhus  patients  during  first  days 
of  the  rash,  and  also  in  trench  fever.  Had 
never  found  organism  in  other  diseases. 

I9I7 

Werner  and  Benzler 

In  the  stomach  of  lice  fed  upon  cases  of 
febrisquintana. 

I918 

Brumpt 

53  out  of  72  body  lice  taken  from  healthy 
prisoners  of  war,  pure  culture  found  in  the 
alimentary  canal  and  in  some  cells;  16 
lice  from  healthy  prisoners  of  war  were  all 
infected,  etc. 

I918 

Arkwright,  Bacot,  and  Duncan 

Lice  fed  on  trench-fever  patients.  Normal 
lice  fed  on  persons  not  exposed  to  trench- 
fever  infection  remained  free  from  Rick- 
ettsia. 

1914 

Rabinowitsch 

In  1908  discovered  Diplobacillus  exantbe- 
Tnaticus  as  the  causative  agent  of  typhus. 
Organism  found  in  blood  of  typhus  pa- 
tients. 

I9I3 

MULLER 

Blood  of  typhus  fever  cases,  inoculated  mice 
and  rabbit. 

I918 

KuCZYNSKI 

In  the  petechia  of  typhus  cases,  in  sections  of 
liver  in  the  endothelial  cells  of  the  capil- 
laries, and  in  free  phagocytic  cells. 

Our  studies  regarding  the  occurrence  of  Rickettsia  bodies  in 
lice  which  have  fed  upon  healthy  persons  have  confirmed  those  of 
a  number  of  observers  already  referred  to.  Lice  collected  from 
healthy  men  in  different  parts  of  France  where  neither  typhus  fever 
nor  trench  fever  were  present  were  often  found  to  contain  Rickettsia 
in  their  dejecta,  from  20  to  40  per  cent  of  such  lice  examined,  col- 
lected in  diflferent  groups,  revealing  these  bodies.  In  some  of  these 
normal  lice,  microscopical  examination  of  the  excreta  or  material 
from  the  ahmentary  tract  showed  them  to  be  severely  infected  with 
Rickettsia  bodies.  Others  were  only  moderately  or  very  slightly 
infected,  while  in  the  remainder  no  definite  Rickettsia  were  ob- 
served. Obviously,  from  a  microscopical  examination,  it  is  some- 


Fig.  I. 


Fig.  2. 
Plate  I. — Richettsia  Bodies  in  the  Excrement  of  Normal  Lice. 


THE   SIGNIFICANCE   OF   RICKETTSIA  121 1 

times  extremely  difficult  to  say  whether  these  bodies  are  not  present 
in  small  numbers  in  the  lice.  In  Plate  I,  Figs,  i  and  2  demonstrate  the 
Rickettsia  bodies  in  the  excrement  of  normal  lice.^  The  lice  are 
referred  to  as  normal  because  they  produced  no  disease  either  in 
their  original  host,  from  which  they  were  collected,  or  when  they 
were  placed  upon  or  fed  upon  other  healthy  individuals. 

A  critical  examination  of  the  literature  regarding  the  relation 
of  Rickettsia  to  disease  reveals  the  fact  that  these  bodies  have  been 
found  in  lice  which  have  fed  upon  cases  of  typhus  fever,  Wolhynian 
fever,  trench  fever,  war  nephritis,  malaria,  bronchitis,  inflammation 
of  the  bladder,  and  inguinal  hernia,  as  well  as  in  a  large  number  of 
lice  collected  in  diff"erent  parts  of  the  world  which  have  fed  only  on 
healthy  people,  in  whom  they  produced  no  disease.  It  is  true  that  in 
lice,  Rocha-Lima  suggests  that  Rickettsia  prowazekiy  which  is  re- 
garded by  him  as  the  probable  cause  of  typhus  fever,  differs  from 
Rickettsia  pediculi,  which  is  found  in  Hce  not  infected  with  the  virus 
of  typhus,  in  that  the  latter  does  not  occur  normally  in  the  epithe- 
lium of  the  alimentary  canal  of  the  louse.  However,  Toepfer,  Brumpt, 
and  others,  as  we  have  seen,  have  found  Rickettsia  in  the  intestinal 
epithelial  cells  of  lice  fed  upon  healthy  individuals,  as  well  as  in 
those  fed  upon  Wolhynian  fever  cases  and  cases  of  war  nephritis. 
Rickettsia  have  also  been  found  in  ticks  that  have  fed  upon  cases  of 
Rocky  Mountain  spotted  fever.  They  have,  in  addition,  been  ob- 
served in  the  blood  of  man  in  a  number  of  diseases — for  example, 
in  typhus  fever,  in  Rocky  Mountain  spotted  fever,  in  Wolhynian 
fever,  and  in  trench  fever.  Rocha-Lima  also  believes  that  he  has 
seen  in  the  blood  of  healthy  persons  bodies  similar  to  those  observed 
in  the  blood  of  Wolhynian  fever  by  other  investigators,  and  described 
by  them  under  the  name  of  Rickettsia. 

Further,  when  we  come  to  consider  the  etiological  significance  of 
Rickettsia  in  human  disease,  it  is  apparent,  from  the  evidence 
already  presented  in  this  article,  that  not  one  of  the  three  classical 
postulates  regarded  necessary  for  the  proof  of  the  etiological  factor 
of  an  infectious  disease  is  fulfilled  by  the  Rickettsia,  (i)  They  have 
not  been  found  in  every  case  of  the  disease  they  have  been  said  to 

1  These  photomicrographs  were  kindly  made  at  the  Pasteur  Institute  by  Dr.  P. 
Jeantet,  who  is  in  charge  of  the  photomicrographic  work  of  this  Institute.  I  wish  to 
express  my  thanks  both  to  Dr.  Roux,  the  Director  of  the  Pasteur  Institute,  and  to  Dr. 
Jeantet  for  this  courtesy. 


I2I2         THE   SIGNIFICANCE   OF   RICKETTSIA 

cause;  moreover,  they  have  been  found  in  connection  with  other 
diseases  than  the  one  of  which  it  is  contended  they  are  the  source. 
(2)  They  have  not  been  isolated  and  grown  in  pure  culture.  (3)  The 
disease  which  they  are  said  to  cause  has  not  been  produced  by  the 
inoculation  of  such  culture. 

It  is  very  possible  that  the  Rickettsia  bodies  are  micro-organisms, 
but  as  they  have  been  found  in  Hce  from  patients  with  so  many 
different  diseases,  as  well  as  in  hce  from  healthy  individuals,  ob- 
viously no  specificity  for  them  can  be  justly  claimed  at  the  present 
time.  It  is  true  that  Rocha-Lima,  Toepfer,  and  Olitsky,  Denzer,  and 
Husk  claim  to  have  produced  typhus  infection  in  animals  by  the 
inoculation  of  the  contents  of  the  alimentary  tract  of  infected  lice. 
In  this  connection  Rocha-Lima  claimed  that  the  disease  developed 
in  the  inoculated  animal  because  the  Rickettsia  were  present  in 
the  lice  used  for  the  injections,  while,  on  the  other  hand,  OHtsky, 
Denzer,  and  Husk  claim  the  disease  developed  because  the  Plotz 
bacillus  was  present  in  the  lice  used  in  the  inoculation  of  the  animals. 
Obviously  we  can  draw  no  definite  conclusions  from  these  experi- 
ments save  that  the  infecting  agent,  visible  or  invisible,  was  present 
in  the  lice.  Nothing  can  be  said  from  them  regarding  the  definite 
nature  of  the  infecting  agent.  Seargent,  Foley,  Vialette,  and  Brumpt 
all  pointed  out  that  the  Rickettsia  might  merely  accompany  the 
infectious  agent. 

Some  further  light  has  recently  been  thrown  upon  the  significance 
of  the  Rickettsia  by  observations  and  experiments  which  we  have 
made  in  connection  with  trench  fever.  In  relation  to  the  etiology 
of  trench  fever,  as  has  been  the  case  in  the  history  of  most  infectious 
diseases,  a  number  of  widely  differing  micro-organisms  have  pre- 
viously been  described  as  its  cause,  but  none  of  these  claims  has  been 
substantiated,  and,  although  very  extensive  studies  have  been  made 
by  a  large  number  of  observers,  it  is  still  a  question  whether  the 
organism  causing  trench  fever  has  yet  been  definitely  seen  in  man, 
either  with  the  microscope  or  the  ultramicroscope.  Our  experi- 
ments, carried  on  in  relation  to  the  etiology  of  trench  fever,  have 
since  shown  that  this  disease  is  caused  by  a  filterable  virus,  which 
bears  some  resemblance  in  its  behavior  to  the  filterable  virus  of 
hog  cholera  (4).  Our  work  regarding  the  filterable  qualities  of  the 
virus  of  trench  fever  has  recently  been  confirmed  by  Major-General 


THE   SIGNIFICANCE   OF   RICKETTSIA         1213 

Sir  John  Rose  Bradford,  Captain  E.  F.  Bashford,  and  Captain  J. 
A.  Wilson  (5).  The  organism  causing  trench  fever,  being  so  minute, 
is  obviously  separated  only  with  great  difficulty  from  the  sur- 
rounding structures  in  the  media  in  which  it  occurs  naturally. 
Thus,  while  we  have  demonstrated  that  the  virus  of  trench  fever  is 
present  free  in  the  plasma  of  the  blood  of  trench-fever  cases,  in  the 
febrile  stages  of  the  disease  it  is  frequently  very  difficult  to  separate 
it  from  the  blood  corpuscles  themselves  by  repeated  washings  of 
these  with  saline  solution  (6).  Also,  in  the  ahmentary  canal  of  the 
louse  fed  upon  trench-fever  cases  and  in  infected  louse  excrement, 
the  virus,  on  account  of  its  minute  size,  is  closely  intermingled  with 
other  cellular  structures  present. 

We  have  also  emphasized  the  fact  that  in  different  examinations 
of  lice  fed  only  upon  healthy  individuals,  the  Rickettsia  have  been 
demonstrated  in  from  20  to  74  per  cent.  Knowing  these  facts,  let 
us  suppose  that  lice  already  containing  such  Rickettsia  in  variable 
number  had  been  fed  upon  trench-fever  cases  and  had  become  in- 
fected with  the  virus  of  trench  fever,  and  such  lice  (containing 
the  Rickettsia,  which  may  in  the  meantime  have  multiphed  or 
increased  in  number)  were  then  placed  upon  healthy  human  beings, 
whom  they  subsequently  infected  with  trench  fever,  obviously, 
then,  erroneous  conclusions  might  be  drawn  that  the  Rickettsia 
were  themselves  the  etiological  factor  of  trench  fever.  It  is  evident 
that  great  difficulty  would  be  experienced  in  a  separation  of  the 
virus  of  trench  fever  from  such  bodies  under  the  circumstances 
described  above.  Probably  only  by  successful  filtration  experi- 
ments such  as  we  have  performed  with  lice  excrement  in  connection 
with  trench  fever  could  the  separation  be  accomplished. 

It  may,  of  course,  be  argued  that  Rickettsia  have  a  filterable 
stage,  as  have  other  so-called  Chlamydozoa,  and  this  idea  receives 
some  support  from  the  fact  that  the  virus  of  trench  fever  is  under 
some  circumstances  filterable  with  difficulty,  and  attempts  to  infect 
human  beings  with  the  filtrates  of  infected  material  are  often  unsuc- 
cessful. Thus  in  10  filtration  experiments  performed  with  infected 
blood  and  urine  from  trench-fever  cases,  and  infected  louse  excre- 
ment, only  3  gave  undoubted  positive  results. The  temperature  charts 
of  2  cases  of  trench  fever,  experimentally  produced  by  the  injection  of 
the  filtered  trench-fever  virus,  are  illustrated  in  Plates  II  and  III. 


I2I4 


THE   SIGNIFICANCE   OF   RICKETTSIA 


THE   SIGNIFICANCE   OF   RICKETTSIA         1215 

Bradford,  Bashford,  and  Wilson  (7)  have  since  reported  upon 
the  cultivation  of  the  trench-fever  virus  from  filtrates  which  have 
previously  passed  through  porcelain  filters,  and  have  also  shown 
by  human  experiments  that  such  filtrates  contain  the  infections 
agent. 

It  is  conceivable  that  the  Rickettsia,  whether  they  possess  a 
filterable  stage  or  not,  may  be  parasites  of  lice  and  not  pathogenic 
for  man,  and  Brumpt  has  suggested  that  the  finding  of  them  in 
human  blood  may  simply  be  an  indication  that  the  individual  has 
been  previously  infested  with  lice.  On  the  other  hand,  there  is  the 
possibility  that  the  bodies  sometimes  described  as  Rickettsia  may 
constitute  products  of  degenerated  cells — for  example,  basophilic 
gradules,  which  are  more  numerous  in  the  blood  in  certain  febrile 
diseases,  in  which  case  they  would  also  increase  in  number  in  the 
lice  fed  upon  such  cases,  and  might  then  merely  accompany  the 
very  minute  or  invisible  etiological  factor  of  the  disease. 

In  connection  with  the  significance  of  Rickettsia  as  an  etio- 
logical factor  in  typhus,  trench  fever,  and  other  diseases,  it  may  be 
of  interest  to  recall  that  in  1903  an  organism  described  by  Parker, 
Beyer,  and  Pothier  as  Myxococcidium  stegomyiae  was  found  in 
infected  stegomyia  mosquitoes,  and  was  for  a  time  supposed  by 
these  investigators  to  be  the  parasite  causing  yellow  fever.  Later 
this  organism  was  found  to  be  a  species  of  yeast,  and  to  occur  not 
only  in  mosquitoes  infected  with  the  virus  of  yellow  fever,  but  also 
in  those  not  infected  with  such  virus,  and  the  virus  of  yellow  fever 
was  shown  to  be  filterable  and  ultramicroscopic.  Noguchi's  (8) 
recent  experiments,  however,  suggest  that  the  organism  of  yellow 
fever  may  be  a  spirochsete  which  is  filterable  at  least  at  one  stage  of 
its  life  history. 

From  a  review  of  the  evidence  presented  in  this  paper  regarding 
Rickettsia,  it  appears  obvious  that,  until  more  definite  results  are 
obtained  from  further  experimental  work,  we  are  not  justified  in 
concluding  that  the  Rickettsia  have  a  definite  specific  etiological 
significance  in  relation  to  human  disease. 


I2i6        THE   SIGNIFICANCE   OF   RICKETTSIA 

BIBLIOGRAPHY 

1.  Arcb.  J.  Protistenk.,  1907,  X,  336. 

2.  "Handbuch  de  Pathogenen  Protozoen,"  Leipzig,  191 1,  Prowazek  and 

others. 

3.  Minchen,  "Introduction  to  the  Study  of  the  Protozoa,"  London,  1917, 

472. 

4.  "Trench  Fever;  Report  of  Commission  of  American  Red  Cross  Re- 

search Committee,"  Oxford,  191 8. 

5.  Bradford,  Bashford,  and  Wilson:  Brit.  M.  J.,  1919,  127. 

6.  Loc.  cit.,  "Trench  Fever  Report,"  27. 

7.  Bradford,  Bashford,  and  Wilson,  loc.  cit. 

8.  Noguchi,  J.  Am.  M.  Ass.,  19 19,  LXXII,  187. 


THE  RELATIVE  INFREQUENCY  OF  CANCER  OF  THE 
UTERUS  IN  WOMEN  OF  THE  HEBREW  RACE 

By  Hiram  N.  Vineberg,  M.D.,  C.M.F.A.C.S.,  New  York 

IN  a  short  paper  on  the  "Etiology  of  Cancer  of  the  Pelvic  Organs," 
read  before  the  New  York  Obstetrical  Society  (i),  January  9, 1906, 
the  writer  drew  attention  to  an  observation  he  had  made  during 
a  service  of  fifteen  years  in  Mount  Sinai  Hospital  Dispensary. 
Although  the  service  was  a  large  one,  visited  by  the  class  of  women 
that  ordinarily  should  furnish  a  fairly  large  number  of  cases  of 
cancer  of  the  uterus,  he  was  struck  with  the  rarity  with  which  that 
disease  was  encountered.  Being  cognizant  of  the  almost  universal 
opinion  that  laceration  of  the  cervix  was  a  potent  cause  of  cancer 
of  that  organ,  he  paid  especial  attention  to  all  cases  with  reference 
to  that  point.  Every  case  presenting  the  slightest  suspicion  of 
malignancy  was  subjected  to  a  thorough  examination  and  kept 
under  observation  for  a  long  period  afterwards  to  determine  the 
correctness  of  the  microscopic  report.  It  may,  therefore,  be  fair  to 
assume  that  very  few  cases  escaped  detection.  This  assumption 
receives  further  confirmation  from  the  fact,  to  which  the  writer  has 
frequently  drawn  attention,  that  it  is  very  rare  indeed  that  one 
meets  with  cancer  of  the  cervix,  especially  of  the  vaginal  portion, 
the  most  common  variety,  in  which  the  diagnosis  is  not  unmistakable 
on  palpation  and  inspection  with  the  naked  eye.  In  other  words, 
when  cancer  of  the  cervix  gives  rise  to  symptoms,  it  is  almost 
always  so  far  advanced  that  the  diagnosis  is  p>ositive  without  the  aid 
of  the  microscope.  The  suspicious  cases,  as  a  rule,  with  very  few 
exceptions,  prove  not  to  be  such.  That,  at  least,  has  been  the 
writer's  experience  and  that  of  a  good  many  other  gynecologists 
with  whom  he  has  spoken. 

The  data,  therefore,  regarding  this  point,  which  the  writer 
collected  from  his  Dispensary  service  from  1893  to  1906,  a  p>eriod 
of  thirteen  years,  may  be  regarded  as  approximately  accurate. 
There  were  during  this  period  19,800  new  patients.  Among  these 

1217 


I2i8    CANCER  OF  THE  UTERUS  IN  HEBREW  WOMEN 

there  were  1995,  or  about  10  per  cent,  with  marked  laceration  of  the 
cervix.  There  were  in  all  18  cases  of  cancer  of  the  cervix.  Here  comes 
the  strikingly  interesting  point:  Roughly  speaking,  95  per  cent  of 
the  patients  were  of  the  Hebrew  religion  and  natives  of  Russia, 
Austria,  and  Poland.  Still  of  the  18  cases  of  cancer  of  the  cervix 
only  9  cases,  50  per  cent,  occurred  among  this  class  of  patients,  while 
the  other  9  cases  were  met  with  among  the  non-Jewish  women,  who 
constituted  only  5  per  cent  of  the  patients.  Consequently  the 
incidence  of  cancer  of  the  cervix  was  twenty  times  greater  in  the 
non-Jewish  than  in  the  Jewish  women.  When  one  stops  to  consider 
that  of  the  total  number  of  the  Jewish  women  1995  had  badly 
lacerated  cervices,  that  they  were  all  immigrants  who,  according 
to  Max  Schiiller,  (2)  show  a  much  greater  predisposition  to  cancer 
than  do  the  natives,  and  that  they  were  hving  in  the  worst  possible 
hygienic  surroundings,  amidst  the  greatest  squalor  and  privation, 
such  as  obtain  in  the  lower  East  Side  of  the  Metropohs,  it  is  truly 
remarkable  that  so  few  cases  of  cancer  of  the  cervix  were  detected 
amongst  them. 

My  associate  and  friend,  Dr.  I.  C.  Rubin,  made  a  painstaking 
investigation  of  the  cases  in  all  of  the  gynecological  services  in 
Mt.  Sinai  Dispensary  from  December,  1909,  to  December,  1918 — a 
period  of  nine  years. 

The  total  number  of  new  cases  examined  approximated  30,000.  Total 
number  of  positive  cases  of  cancer  of  the  cervix  was  20.  Total  number  of 
suspected  but  not  established  cases  of  cancer  of  the  cervix  was  50.  This 
included  hypertrophied,  eroded,  ulcerated,  and  bleeding  cervices  in  which 
subsequent  control  failed  to  establish  cancer,  or  in  which  curettage,  partial 
excision  of  the  cervix  for  diagnostic  purposes  and  hysterectomy  did  not 
result  in  a  positive  finding  of  cancer.  The  proportion  of  cases  of  cancer  of 
the  cervix  in  this  material  was  therefore  20  in  30,000,  or  i  in  1500  cases. 
Of  these  20  cases  13  were  in  Jewish  women  and  7  in  non- Jewish  women. 
The  7  non- Jewish  women  were  either  Americans  or  of  the  Slavic  immigrant 
class. 

The  general  proportion  of  non-Jewish  to  Jewish  women  at  the  Dis- 
pensary during  this  period  was  about  one  in  15,^  consequently  the  actual 
incidence  of  cancer  of  the  cervix  in  the  Jewish  patients  of  the  Dispensary 
was  13  in  28,000,  or  i  in  2154  cases.  In  the  non-Jewish  women  it  was  7  to 
2000,  or  I  in  285,  or  7j^  times  greater  than  in  the  Jewish  women. 

1  Based  on  an  actual  count  for  two  years  of  the  period. 


CANCER  OF  THE  UTERUS  IN  HEBREW  WOMEN      1219 

It  is  interesting  to  note  the  close  ratio  of  the  incidence  of  cancer  of 
the  cervix  in  the  Jewish  women  in  the  two  series,  that  of  1893- 1906  and 
of  1909-18,  In  the  one  it  was  one  in  2089  cases,  in  the  other  one  in  2154 
cases.  But  the  ratio  in  the  non- Jewish  women  shows  a  marked  difference. 
In  the  first  series  it  was  one  in  1 1 1  cases,  in  the  second  series  it  was  one  in 
285  cases. 

Dr.  Rubin  investigated  also  the  records  of  the  Mt.  Sinai  Hospital 
during  the  same  period.  From  December,  191 1,  to  December,  19 18,  there 
were:  Carcinoma  of  the  cervix,  58  cases;  of  the  uterus,  35  cases;  of  the  va- 
gina, 5  cases.  The  total  number  of  patients  admitted  to  the  Gynecological 
Department  during  this  period  was  approximately  7000.  The  total  numt)er 
of  adult  females  admitted  to  the  hospital  during  the  same  period  was 
30,000.  As  each  of  these  patients  was  subjected  to  a  thorough  and  care- 
ful physical  examination  as  a  matter  of  routine,  and  wherever  the  slightest 
suspicion  existed  a  special  gynecological  examination  was  added  by  one 
of  the  attending  gynecologists,  it  is  quite  natural  that  the  percentage  of 
cancer  of  the  cervix  would  be  much  higher  than  in  the  dispensary  cases. 
The  difference  in  the  ratio  can  further  be  explained  by  the  fact  that  prac- 
tically only  op>erative  cases  are  admitted  to  the  gynecologictd  services  of 
the  hospital. 

But  the  point  that  has  a  special  bearing  upon  our  contention  is  the 
ratio  existing  between  the  non-Jewish  and  Jewish  women.  Of  the  65  cases 
of  cancer  of  the  cervix  32  were  in  Jewish  and  33  in  non- Jewish  women. 
As  the  same  ratio  obtains  in  the  hospital'  as  in  the  disp)ensary,  that  is,  i 
to  15,  the  general  incidence  would  be  for 

Jewish  women,  32  to  28,000,  or  i  in  937  cases. 

Non- Jewish  women,  33  to    2,000,  or  i  in    61  cases. 
The  incidence  therefore  is  fifteen  times  greater  in  the  non-Jewish  patients 
than  in  the  Jewish  patients  treated  in  the  hospital. 

Occurrence  oj  Carcinoma  in  Other  Viscera.  For  this  purix)se  the  year 
December,  19 17,  to  December,  191 8,  was  chosen. 

Carcinoma  of  the  rectum,  23  cases:  Jewish,  21;  non-Jewish,  2.  In  this 
series  there  were  9  in  females  and  14  in  males. 

Carcinoma  of  the  intestines,  23  cases:  11  in  females,  12  in  males,  19 
Jewish,  4  non- Jewish,  of  which  3  were  females. 

Carcinoma  of  the  stomach,  43  cases:  18  females,  25  males,  37  Jewish, 
6  non- Jewish,  4  women  and  2  men. 

Carcinoma  of  the  breast,  1 7  cases :  6  non- Jewish. 

Contrasted  with  the  occurrence  of  carcinoma  in  other  organs  than  the 
uterus,  it  appears  that  carcinoma  of  the  cervix  is  a  little  more  than  eight 

*  Based  on  an  actual  count  for  two  years  of  the  period  the  same  as  for  the  dispensary. 


1220     CANCER  OF  THE  UTERUS  IN  HEBREW  WOMEN 

times  as  infrequent  as  carcinoma  of  the  rectum ;  eight  times  as  infrequent 
as  carcinoma  of  the  intestines,  exclusive  of  the  rectum;  sixteen  times  as 
infrequent  as  carcinoma  of  the  stomach,  and  about  seventeen  times  as  in- 
frequent as  carcinoma  of  the  breast. 

In  other  words,  there  are  treated  as  many  cases  of  carcinoma  of  the 
rectum  or  of  the  intestines  in  one  year  at  Mt.  Sinai  Hospital  as  there  are 
carcinoma  of  the  cervix  uteri  cases  in  eight  years,  and  twice  as  many 
stomach  cancer  cases  in  one  year  as  there  are  cancer  cervix  cases  in  eight 
years. 

This  is  highly  significant  in  view  of  the  fact  based  on  statistics  (refer- 
ences to  which  occur  later)  that  in  the  relative  frequency  of  cancer  of  the 
individual  organs,  that  of  the  uterus  stands  first  in  the  list. 

The  writer  has  made  a  search  of  the  literature  and  found  but 
very  meager  references  to  the  subject.  What  he  did  find  was  all 
confirmatory.  After  the  time  the  writer  made  the  observations 
here  under  discussion  he  interrogated  several  colleagues  who  were 
likely  to  come  into  contact  with  the  same  class  of  patients.  They  all 
said  that  since  their  attention  had  been  drawn  to  it,  they  recalled 
that  their  experience  corresponded  with  his  own. 

A.  Theilhaber  (3)  draws  attention  to  the  slight  disposition  of 
Jewesses  to  cancer  of  the  cervix.  In  228  cases  of  fibromyoma  49 
(19. 1  per  cent)  were  Jewesses;  in  133  cases  of  cancer  of  the  cervix 
only  I  (0.75  per  cent)  was  a  Jewess.  He  learned  that  this  experience 
was  confirmed  by  others. 

F.  Theilhaber  (4)  states  that  disease  statistics  in  Germany  are 
not  classified  according  to  religion.  But  such  a  classification  exists 
in  the  city  of  Budapest.  In  that  city  the  Jews  are  fairly  equally 
divided  among  all  classes  of  inhabitants.  They  show  a  marked 
increase  of  births  over  the  others.  He  furnishes  statistics  to  demon- 
strate that  the  number  of  childbirths  have  a  bearing  upon  cancer  of 
the  cervix. 


No.  OF  Births 

Cancer  of  the  Cervix, 
Per  Cent 

Fibromyoma, 
Per  Cent 

0 

4 

39 

1 

13 

19 

2 

15 

13 

3-  5 

33 

19 

6-  8 

15 

9 

9-10 

10 

1 

11-15 

10 

0 

CANCER  OF  THE  UTERUS  IN  HEBREW  WOMEN      1221 

Hofmeier  and  others  have  published  statistics  demonstrating  a 
similar  ratio  between  the  number  of  childbirths  and  the  occurrence  of 
cancer  of  the  cervix. 

Theilhaber  emphasizes  the  significance  of  the  fact  that  Jewesses 
reach  an  older  age  than  do  other  Budapest  women.  Hence  their 
participation  in  all  diseases  in  which  age  bears  an  influence  should 
be  greater.  He  states  that  the  mortality  among  Jewish  children  is 
much  less  than  among  other  children.  This,  of  course,  as  a  natural 
consequence  advances  the  age  of  the  Jewish  population,  so  that 
under  the  Jewish  deaths  almost  double  as  many  old  people  are  to  be 
found  as  under  the  deaths  of  all  the  other  population. 

To  quote  further  from  Theilhaber's  paper,  in  the  year  1906 
there  were  in  all  16,360  deaths  in  Budapest,  among  which  were  2500 
Jews,  or  15  per  cent;  27  per  cent,  excluding  cancer  of  the  uterus, 
died  of  cancer,  but  only  8.05  per  cent  died  of  cancer  of  the  uterus; 
thus  there  were  only  one-third  of  the  number  which  one  would 
expect  from  the  cancer  deaths  in  toto. 

DEATHS  IN  BUDAPEST 


Year 

Total 
Deaths 

Jewish 
Deaths 

Total 
Cancer  Deaths 

Jewish 
Cancer  Deaths 

1906 

16,380 

2,500 

785 

183 

1905 

16,094 

2,623 

867 

153 

1904 

15,435 

2,614 

1,009 

192 

1903 

15,059 

2,468 

896 

188 

1902 

14.732 

2,400 

869 

167 

DEATHS  FROM  CANCER  OF  UTERUS 


Year 

Total 

Jewesses, 
Per  Cent 

Jewish 

Cancer  Deaths 

Per  Cent 

1906 

149                            12—  8 

23  3 

1905 

142               1               IS— 10. 5 

17 

1904 

170 

13—  7-7 

19 

1903 

150 

18—12 

209 

1902 

172               1               10—  5  8 

19. 1 

1               783               1               6&—  8-7 

19. 5 

There  is  no  separation  in  the  above  statistics  of  cancer  of  the  cervix  from  that  of 
the  body,  so  that  many  of  the  cases  may  have  been  cancer  of  the  body. 

Theilhaber  quotes  from  H.  Kirschner  unpublished  data  in  ref- 
erence to  the  city  of  Munich.  In  that  city  from  1876  to  1908  there 
died  185  Jews  from  cancer,  of  these  there  were  98  women.  Seven  of 


1222     CANCER  OF  THE  UTERUS  IN  HEBREW  WOMEN 

these  had  cancer  of  the  uterus,  so  forming  only  7  per  cent  of  the 
cancer  cases  in  the  Jewish  women.  The  usual  ratio  of  cancer  of  the 
uterus  is  from  25  per  cent  to  35  per  cent  of  all  cases  of  cancer.  That 
the  Jewesses  of  Munich  did  not  show  such  relative  immunity  from 
cancer  of  other  organs  is  evidenced  by  the  fact  that  during  the  same 
period  41  died  of  cancer  of  the  stomach  and  of  the  intestines. 

Birch-Hirschfeld  has  asserted  that  the  relative  frequency  of 
cancer  of  the  individual  organs  may  be  stated  according  to  the  fol- 
lowing scale:  i,  Uterus;  2,  external  skin;  3,  mamma;  4,  stomach. 

A.  Theilhaber  and  S.  Greischer  (5)  furnish  further  statistics  from 
Munich  and  Niirnberg: 

Munich,  1907-1909 

Christians 

Per  cent 

Total  No.  of  deaths 1326  

No,  of  deaths  from  cancer  of  uterus  and 

mamma 501  37-7 

No.  of  deaths  from  cancer  of  uterus 381  28. 7 

No.  of  deaths  from  cancer  of  mamma 120  9 

Jewesses 

Total  No.  of  cancer  deaths 102  23 . 5 

No.  of  deaths  from  cancer  of  uterus 7  6.8 

No.  of  deaths  from  cancer  of  mamma 17  16.7 

NURNBERG,   I907-I909 

Jewesses 

Total  No.  of  cancer  deaths 30  .... 

No.  of  deaths  from  cancer  of  uterus  and 

mamma 6  20 

No.  of  deaths  from  cancer  of  uterus i  3.3 

No  of  deaths  from  cancer  of  mamma 5  16.6 

It  will  thus  be  seen  that  in  Munich  the  percentage  of  deaths  from 
cancer  of  the  uterus  among  Jewesses  was  but  one-fifth  of  those 
among  the  Christians.  On  the  other  hand,  the  percentage  of  deaths 
from  cancer  of  the  mamma  among  Jewesses  was  nearly  double  as 
great  as  that  among  Christian  women. 


CANCER  OF  THE  UTERUS  IN  HEBREW  WOMEN     1223 

The  writer  consequently  believes  that  the  fact  has  been  fully 
established  that  cancer  of  the  cervix  of  uterus  is  much  less  frequently 
met  with  among  Jewesses,  particularly  of  those  belonging  to  the 
poorer  classes  and  hence  among  the  most  orthodox,  than  among 
the  women  of  the  Christian  religion. 

The  fact  has  also  been  established  that  so  far  as  cancer  of  the 
other  organs  is  concerned  no  such  immunity  exists.  On  the  con- 
trary, if  anything,  statistics  demonstrate  that  Jewesses  are  more 
prone  to  cancer  of  the  other  organs  than  are  their  Christian  sisters. 

The  question  now  arises,  to  what  factor  or  factors  may  be  attrib- 
uted the  comparative  immunity  of  this  particular  organ?  What 
is  there  in  their  mode  of  living  and  habits  that  stands  out  promi- 
nently as  being  different  from  the  poorer  classes  of  other  religions? 
No  explanation,  as  far  as  the  writer  is  aware,  has  been  offered  by  any 
of  the  authors  who  have  written  on  the  subject.  We  know  that 
whatever  differences  there  may  exist  regarding  squalor,  p)overty, 
and  unhygienic  surroundings  are  not  in  their  favor. 

The  writer  himself  in  the  article  referred  to  ventured  an  expla- 
nation. It  occurred  to  him  that  the  only  marked  difference  in  their 
mode  of  living  and  habits  from  that  of  the  women  of  most  all  other 
religions  consisted  in  their  strict  observance  of  the  Mosaic  Law 
regarding  marital  relations.  Sexual  congress  is  prohibited  during 
menstruation  and  during  seven  days  following  the  cessation  of  the 
flow.  The  Mosaic  Law'  commands  that  the  woman  count  seven 
unclean  days  (whether  the  flow  lasts  that  long  or  not)  and  seven 
clean  days  before  she  takes  the  bath  of  immersion  and  marital  rela- 
tions are  resumed.  If  the  flow  should  f>ersist  for  more  than  seven  days 
or  return  before  the  count  of  the  seven  clean  days  had  elapsed,  the 
count  of  the  seven  clean  days  must  begin  anew.  Thus  in  cases  of 
menorrhagia  or  metrorrhagia  sexual  intercourse  might  not  be  f>er- 
mitted  for  months. 

Again  after  parturition  the  Mosaic  Law*  enjoins  abstinence  from 
the  sexual  act  for  a  variable  period,  depending  upon  whether  the 
birth  was  of  a  male  or  female  child.  My  learned  friend  Dr.  D.  de 
Sola  Pool  states  that  these  laws  are  only  the  starting  points  for  an 
extended  development  in  actual  Jewish  life — "one-sixth  of  the  whole 
Talmud  is  given  up  to  laws  of  women,  including  the  laws  of  marriage, 

*  Leviticus  xv,  19  seq.  *  Leviticus  xii. 


1224     CANCER  OF  THE  UTERUS  IN  HEBREW  WOMEN 

divorce,  etc.,  and  the  laws  in  which  you  are  especially  interested." 
He  further  states  the  official  formulation  of  Jewish  law  compiled 
towards  the  end  of  the  Middle  Ages,  which  is  still  the  authoritative 
code  of  traditional  law,  "demands  the  counting  of  fourteen  days 
for  a  male  and  twenty-one  days  for  a  female  child  before  the 
woman  is  permitted  to  her  husband.'*  "There  are  places  where  it 
is  the  custom  not  to  take  the  bath  of  purification  after  childbirth 
until  forty  days  after  the  birth  of  a  son  and  eighty  days  after  the 
birth  of  a  daughter.  It  has  become  the  general  rule  throughout 
Israel  not  to  cohabit  so  long  as  there  is  any  blood  whatsoever, 
even  *clean  blood.*  Therefore,  if  there  is  any  appearance  of  blood 
after  seven  or  fourteen  days,  even  though  the  Biblical  law  allows 
cohabitation,  it  is  customary  to  wait  for  seven  complete  days  after 
the  disappearance  of  the  last  vestige  of  blood  before  allowing 
cohabitation.** 

It  is  well  known  that  the  poorer  classes  of  non- Jewish  women  not 
only  do  not  observe  such  restrictions,  but  are  in  the  habit  of  indulging 
in  cohabitation  during  the  menstrual  period  and  very  shortly  after 
parturition. 

If  there  is  one  thing  in  which  there  is  a  consensus  of  opinion 
regarding  the  etiology  of  cancer  it  is  that  continued  irritation, 
especially  under  unfavorable  conditions,  is  a  potent  causative  fac- 
tor. That  sexual  irritation  under  any  condition  is  a  predisposing 
cause  is  evidenced  by  the  fact,  established  by  all  available  statistics, 
that  cancer  of  the  cervix  is  much  more  common  among  the  married 
and  widowed  than  among  the  non-married. 

Accepting  this  proposition,  then,  it  must  be  granted  that  cohabi- 
tation during  the  menstrual  period  or  immediately  thereafter,  when 
the  uterus  is  still  in  a  high  degree  of  congestion,  must  increase 
markedly  the  harmful  effect  of  the  irritation  of  the  sexual  act  at 
ordinary  times.  It  must  be  borne  in  mind,  in  consequence  of  their 
adherence  to  the  Mosaic  Code,  the  orthodox  Jewish  woman  is 
subjected  to  this  irritation  of  the  sexual  act  for  practically  only 
two  weeks  out  of  four.  And  that  in  cases  of  metrorrhagia  (having 
to  count  seven  clean  days)  the  sexual  act  may  not  be  allowed  for 
months  at  a  time.  That  sexual  intercourse  after  parturition  before 
the  bloody  discharge  has  ceased  must  cause  hyperirritation  must 
also  be  granted. 


CANCER  OF  THE  UTERUS  IN  HEBREW  WOMEN     1225 

The  writer  is  fully  aware  that  the  theory  he  offers  does  not  per- 
mit of  substantiation  by  scientific  exjjerimentation.  But  in  our 
present  ignorance  of  the  cause  of  cancer  a  collection  of  carefully 
sifted  clinical  data  regarding  an  organ  ordinarily  prone  to  cancer 
may  prove  of  some  value  in  the  solution  of  the  problem  of  cancer 
etiology. 

BIBLIOGRAPHY 

1.  Am.  J.  Obst.,  1906,  LIII,  410. 

2.  Arcb.  /.  Rassen-  u.  Gesellscb.  Biol.,  Bd.  I,  1904. 

3.  MUncben.  med.  Wcbnscbr.,  $6,  No.  25. 

4.  "Zur  Lehre  von  dem  Zusammenhang  das  Sozialen  Stellung  und  der 

Rasso  mit  der  Entstehung  der  Uterus  Carcinoma,"  Ztscbr.  J.  Krebs- 
Jorscb.,  1909-1910,  VIII,  460.  / 

5.  Ztscbr.  J.  Krebsjorscb.,  1910,  X,  530.  /^ 


THE  CONTRIBUTION  OF  MODERN  PSYCHIATRY  TO 
GENERAL  MEDICINE 

By  William  A.  White,  M.D.,  Washington,  D.  C. 

THE  history  of  psychiatry,  hke  the  history  of  all  scientific 
progress,  has  been  a  history,  at  first,  of  attempts  to  describe, 
to  set  forth,  to  define  the  material  with  which  it  was  con- 
cerned. This  descriptive  stage  in  its  development  has  been,  perhaps, 
unusually  prolonged  because  of  the  great  complexity  of  the  problems 
involved  and  the  inadequacy  of  the  existing  knowledge  of  the  nature 
and  meaning  of  the  human  mind  and  its  placement  in  the  biological 
scheme  of  evolution.  Mind,  the  most  intimate  and  personal  of  our 
possessions,  has,  longer  than  any  other,  resisted  the  application  of 
rigid  scientific  methods,  and  its  pulhng  apart,  its  dissection,  has  been 
resented  for  a  longer  time  and  with  prejudices  equally  as  strong 
as  those  which  offered  such  obstructions  to  the  study  of  human 
anatomy. 

Until  the  present  generation  the  scientific  approach  to  the 
problems  of  mental  disease  was  by  way  of  an  ever-increasing  refine- 
ment of  the  descriptions  of  disease  types.  The  early  descriptions 
had  very  few  concepts  to  work  with  in  this  task,  and  they  were  but 
crude  generalities,  such  as  melancholia,  mania,  and  dementia. 
Upon  this  simple  background  classifications  were  built  which  largely 
tended  to  further  divisions  based  upon  the  content  of  the  delusional 
and  hallucinatory  systems.  With  such  notable  exceptions  as  paresis 
(first  described  by  Wilhs,  1672),  the  attempt  to  formulate  paranoia 
by  Heinroth,  and  later  by  Esquirol  in  his  concept  of  monomania, 
later  followed  largely  by  the  English  school  in  this  particular,  and 
hebephrenia  by  Kahlbaum  (1863),  and  later  by  his  pupil  Hecker 
(1871),  and  the  later  description  of  catatonia  by  Kahlbaum  (1869), 
psychiatry  entered  upon  its  career  at  the  beginning  of  the  present 
generation  with  only  such  a  simple  descriptive  material. 

During  the  latter  part  of  the  nineteenth  century  several  efforts 
were  made  to  expand  beyond  the  limitations  of  such  concepts, 

1226 


PSYCHIATRY  AND  GENERAL  MEDICINE      1227 

notably  by  Ziehen,  who  attempted  a  classification  of  mental  diseases 
based  upon  a  normal  psychology.  But  as  psychology  was  itself  still 
in  the  descriptive  stage  of  its  development,  the  attempt  only  suc- 
ceeded in  further  refinements  of  the  various  classificatory  divisions, 
which  were  soon  found  to  have  Httle  to  commend  them  because 
they  only  rested  upon  superficially  observable  diff"erences.  Wernicke 
attempted  a  neurological  approach  based  upon  analogies  to  aphasia, 
which  also  was  soon  lost  sight  of,  largely,  at  least,  because  of  the 
very  inadequate  knowledge,  then,  as  now,  of  the  real  fundamental 
meanings  to  be  attached  to  this  extremely  complex  and  inadequate 
concept.  Finally  Kraepelin,  by  pushing  the  life  history  method  of 
biology  to  include  the  course  and  outcome  of  the  disease,  its  longi- 
tudinal section  as  opposed  to  the  hitherto  cross-section  method  of 
study,  brought  psychiatry  to  the  last  refinement  of  the  descriptive 
stage  of  its  development. 

While  Kraepelin  was  elaborating  the  description  of  the  psychoses, 
the  French  school,  headed  by  Janet,  was  devoting  its  attention  to  a 
finer  analysis  of  the  neuroses  and  psychoneuroses,  a  movement 
which  was  soon  followed  in  this  country  by  a  recognition  that  the 
place  to  begin,  in  order  to  get  an  understanding  of  mental  illness, 
was  in  the  borderland  region  between  health  and  disease,  a  prin- 
ciple that  was  definitely  incorporated  in  the  program  of  the  Patho- 
logical Institute  of  the  New  York  State  Hospitals.  The  work  done 
by  the  students  of  these  borderland  states  resulted  in  the  formula- 
tion of  the  concept  of  dissociation,  although  the  dynamics  of  disso- 
ciation were  not  adequately  appreciated  and  the  concept,  for  the 
most  part,  was  employed  as  a  still  further  refinement  of  description. 

About  this  time  there  arose  the  behavioristic  school  of  psychol- 
ogists, which  was  the  result  of  attempting  to  study  animal  behavior. 
Inasmuch  as  animals  cannot  be  interrogated  as  a  means  of  access  to 
introspective  material,  the  effort  here  was  to  apply  the  methods  of 
objective  science  to  the  explanation  of  conduct.  The  behaviorists 
accordingly  thought  that  the  best  way  to  answer  the  query  as  to 
what  an  individual  was  doing  was,  not  to  ask  him,  for  his  an- 
swer might  well  be  for  many  reasons  misleading,  but  to  observe,  as  a 
matter  of  fact,  what  he  actually  did  do.  Some  of  the  behavior- 
ists actually  abjure  the  introspective  data  entirely.  Out  of  this 
behavioristic  method  of  approach  have  grown  those  methods  of  mass 


1228      PSYCHIATRY  AND  GENERAL  MEDICINE 

testing,  so  much  used  with  the  military  recruits,  and  those  methods 
of  testing  out  the  fitness  of  individuals  for  special  kinds  of 
work  which  have  received  their  application  in  the  industrial  utiliza- 
tion of  prisoners  and  similar  applications  in  the  field  of  vocational 
psychology. 

About  the  same  time  that  the  behavioristic  program  was  being 
formulated  the  psychoanalytic  school  came  into  prominence  with 
its  exquisite  emphasis  upon  the  individual  material.  It  caught  up 
in  its  principles  both  the  behavioristic  concepts,  and  those  of  the 
French  school  of  Janet  and  its  American  offshoot.  It  laid  particular 
emphasis  upon  the  material  derived  from  introspection,  not  because 
of  its  face  value,  but  because  it  included  certain  facts  of  experience, 
which,  because  they  were  psychological  facts,  were  none  the  less 
facts  and  worthy  of  scientific  attention  and  attempts  at  explanation. 
It,  too,  sought  to  go  beyond  purely  descriptive  aims  and  attempted 
an  interpretation  along  lines  of  dynamic  explanations  which  took 
into  consideration  the  psychological  motives  for  conduct,  not  alone 
those  that  were  obvious,  but  the  deeper-lying  motives  that  could 
be  traced  only  through  an  intimate  knowledge  of  the  lines  along 
which  the  personality  had  developed  and  unfolded  itself.  In  its 
technical  procedure  it  emphasized  the  developmental  aspects  of 
the  psyche  by  attempting,  as  the  term  psychoanalysis  implies,  a 
psychological  analysis,  dissection,  which  would  disclose  the  roots 
through  which  the  symptoms  gained  the  nutrient  material  which 
at  once  called  them  into  being  and  served  to  maintain  them. 

The  important  contributions  of  this  approach  to  the  problems 
of  defective  personal  adjustments  were  the  elaboration  of  the  con- 
cept of  the  subconscious  as  used  by  the  exponents  of  dissociation 
and  the  formulation  of  the  concept  of  the  unconscious  which  was 
conceived  of  as  containing  the  deposits,  so  to  speak,  which  testified 
to  the  history  of  the  development  of  the  psyche,  both  ontogenetic 
and  phylogenetic.  A  study  of  these  deposits  of  the  past  has  by 
analogy  been  termed  paleopsychology  (Jelliff'e).  Added  to  this 
extremely  and  pragmatically  useful  dynamic  concept  of  the  uncon- 
scious is  the  further  concept  of  the  intrapsychic  conflict  which 
explains  development  as  a  progressive  overcoming  of  obstacles,  the 
nature  of  which  determines  the  psychological  deposits,  precipitates, 
that  paleopsychology  uncovers  for  the  purpose  of  discovering  the 


PSYCHIATRY  AND  GENERAL  MEDICINE      1229 

dynamic  elements  which  have  been  operative  in  the  formulation 
of  the  personality. 

The  personality  is  thus  seen  to  be  an  end  product  in  a  continuous 
series  of  developmental  changes,  and  conduct  to  be  the  final  result 
in  action  as  determined  by  the  historical  past  of  the  psyche.  The 
psyche  thus  comes  by  analogy  to  have  both  an  embryology  and  a 
comparative  anatomy,  but  instead  of  bodily  organs  ideas  and  feel- 
ings, a  study  of  the  development  of  which  is  of  equal  importance 
to  its  understanding,  as  are  the  study  of  embryology  and  comparative 
anatomy  to  an  understanding  of  the  bodily  organs. 

The  study  of  individual  reactions  from  this  point  of  view  soon 
disclosed  that  they  have  protective,  defensive,  compromise,  and 
substitutive  functions,  just  as  we  find  reactions  to  have  in  the  realm 
of  the  so-called  organic,  and  thus  from  the  point  of  view  of  their 
meanings,  the  ends  that  they  seek  to  bring  to  pass,  the  distinction 
as  between  so-called  organic,  somatic  reactions  and  so-called  func- 
tional, psychological  reactions  tended  to  be  dissolved,  broken  down, 
as  no  longer  serving  a  useful  purpose. 

This  breaking  down  of  the  ages-old  distinction  between  mind 
and  body  was  but  the  negative  aspect  of  what  soon  became  a 
movement  in  a  positive  direction  to  construct  a  formulation  that 
would  serve  to  explain  the  placement  and  meaning  of  the  psyche 
in  the  developmental  scheme.  It  was  the  beginning  of  a  union  which 
is  already  pregnant  with  great  possibilities. 

The  parallelistic  theory  of  the  relation  of  body  and  mind,  which 
had  occupied  the  stage  for  so  long,  conceived  of  mind  as  something 
which  had  somehow  been  added  in  the  course  of  evolution,  and  seems 
to  hark  back  to  those  medieval  concepts  that  set  man  apart  from 
the  rest  of  animate  creation.  The  psyche,  like  disease,  was  a  sort 
of  visitation  that  came  and  settled  upon  man  from  without,  and 
did  not  seem  to  constitute  an  organic,  structural  part  of  his  being. 
A  study  of  the  development  of  the  lower  forms  of  life  along  the 
lines  suggested  by  Child  has  served  to  demonstrate  that  develop- 
ment has  not  proceeded  by  a  series  of  superpositions.  He  has  shown 
in  his  study  of  the  development  of  certain  fresh-water  planarians 
the  existence  of  what  he  variously  calls  a  dynamic,  irritability, 
or  metabolic  gradient  that  is  a  definite  organization  along  certain 
lines  along  which  the  rate  of  metabolic  changes  showed  a  clear 


1230      PSYCHIATRY  AND  GENERAL   MEDICINE 

tendency  to  vary  in  a  gradually  decreasing  ratio.  Living  beings, 
by  virtue  of  the  very  fact  that  they  are  living  and  are  organized, 
show  the  existence  of  their  organization  in  this  laying  down  of 
gradients,  and  the  main  axial  gradient  shows  from  the  very  first 
a  differentiation  into  a  head  end.  He  further  demonstrated  that 
these  developmental  gradients  are  but  the  organized  interrelations 
of  the  several  parts  of  the  organism  laid  down  in  the  structure  of 
the  gradient.  In  other  words,  the  various  adjustments  which  the 
organism  is  called  upon  to  make  in  its  relation  to  its  environment, 
its  functions,  are  integrated  and  laid  down  in  the  structure  of  its 
several  dynamic  gradients:  "We  must  seek  for  the  integrating 
factor  in  the  relation  between  living  protoplasm  and  its  environ- 
ment." To  illustrate:  let  a  diflPerence  at  some  point  in  the  environ- 
ment act  as  a  stimulus  at  a  given  point  at  the  surface  of  a  bit  of 
protoplasm.  The  immediate  result  is  an  increase  of  activity  at 
this  point  which  activity  is  not  limited  to  the  point  of  application, 
but  spreads  in  ever  widening  waves  such  as  result  when  a  stone  is 
thrown  into  a  quiet  pond.  As  this  wave  of  energy  spreads  there  is 
a  constant  decrement  in  its  effectiveness  so  that  a  dynamic  gradient 
is  established,  the  point  of  greatest  intensity  or  highest  rate  of 
activity  being  the  point  of  the  original  stimulus.  A  passing  stimulus 
produces  only  a  passing  gradient,  while  a  long-continued,  or  often- 
repeated,  or  very  strong  stimulus,  or  all  combined,  tends  to  establish 
permanent  changes  in  the  protoplasm  along  the  path  of  the  in- 
creased activity.  This  dynamic  gradient  becomes  the  starting 
point  of  a  permanent  quantitative  order  in  the  protoplasm  or  a 
physiological  axis.  This  is  the  process  which  I  have  called  the 
structuralization  of  function;  it  is  the  organization  of  past  ex- 
perience made  into  a  stable  foundation  for  further  building.  The 
correlation  of  the  several  parts  of  the  organism,  its  integration, 
is  dynamic,  and  dominance  is  dependent  upon  transmitted  change 
or  excitation  from  the  region  of  highest  metabolic  rate — the  head 
region.  The  nervous  system  is  "the  final  expression  of  relation 
which  is  the  foundation  and  starting  point  of  organic  individuation." 
From  this  dynamic  point  of  view  of  the  constitution  and  de- 
velopment of  the  individual  it  can  be  readily  appreciated  that  it 
is  no  longer  permissible  to  think  of  the  psyche  as  something  which 
has  been  added  in  the  course  of  evolution.  The  history  of  the  psyche, 


PSYCHIATRY  AND  GENERAL  MEDICINE      1231 

far  from  being  relatively  a  short  one  as  compared  to  the  history  of 
the  body  as  ordinarily  conceived,  must  of  necessity  be  of  equal 
length.  Just  as  the  potentialities  of  the  later  developed  heart,  lungs, 
liver,  kidneys,  stomach,  etc.,  were  included  in  the  earliest  reaction, 
mechanisms  of  the  simplest  forms  of  Hfe,  so  also  were  included  the 
potentialities  which  later  manifested  themselves  in  the  highest  forms 
of  psychological  activity. 

The  psyche  as  the  dominant  head  end  of  the  main  axial  gradient 
thus  steps  into  a  position  of  supreme  importance.  The  personaHty, 
far  from  being  a  matter  that  can  be  left  out  of  account  in  the  con- 
sideration of  a  sick  individual,  may  well  be  not  only  of  great,  but 
perhaps  of  the  greatest  importance.  It  is,  to  use  a  crude  analogy, 
the  switchboard  where  all  lines  meet  and  hence  where,  in  the  or- 
ganized scheme  of  the  integrated  individual,  all  somatic,  so-called 
organic  states  reverberate  and  receive  their  final  direction. 

The  attempt  has  been  made  (Adier)  to  interpret  character 
traits,  particularly  as  found  in  the  maladaptations  of  the  neuroses 
and  psychoneuroses,  by  referring  them  to  inferior  organs  the 
inefficiency  of  which  in  the  scheme  of  the  whole  individual  found 
expression  in  the  psyche  as  a  feefing  of  inferiority.  This  feefing  of 
inferiority  caused  the  individual  to  avail  himself  of  certain  dex- 
terities to  compensate  for  and  help  to  overcome  the  feefing  and  these 
mechanisms,  founding  in  certain  organic  deficiencies  of  adjustment, 
produced  the  symptoms. 

This  concept  of  the  psyche,  which  makes  its  development  con- 
temporaneous and  coterminous  with  the  development  of  the  indi- 
vidual as  a  whole  and  all-inclusive  in  its  centralized  relations 
with  the  different  parts,  makes  its  inclusion  in  any  study  of  the 
individual  necessary  if  that  individual  is  to  be  really  understood 
and  any  adequate  attempt  made  to  reconstruct  in  thought  the  indi- 
vidual from  the  point  of  view  of  the  dynamic  factors  which  have 
produced  the  end  result  as  we  see  it  in  the  patient  who  applies  to 
us  for  help.  Whether  the  concept  of  inferior  organs  is  adequate 
to  account  for  all  failures  and  defects  of  adjustment  is  open  to  serious 
question.  It  seems  to  me  to  be  too  anatomical,  too  static  a  concept 
in  some  particulars,  and  while  inferior  organs  are  undoubtedly 
at  the  basis  of  many  grave  character  defects  (cortical  inferiority) 
still,  a  more  dynamic  approach  is  therapeutically  frequently  more 


1232      PSYCHIATRY  AND  GENERAL   MEDICINE 

valuable.  In  the  minor  defects  of  adjustment  it  seems  more  useful 
to  see  the  results  as  flowing  from  the  bad  use  to  which  certain 
mechanisms  have  been  put  in  the  course  of  the  unfolding  personality 
rather  than  to  see  at  the  basis  of  such  defects  an  anatomically 
inferior  organ. 

The  psychoanalysts  have  long  emphasized  the  conflict  be- 
tween the  instinctive  tendencies  and  the  aspirations  as  the  focal 
point  about  which  the  symptoms  of  mental  ilhiess  revolve.  This 
translation  of  the  psychological  symptoms  into  terms  of  energy 
redistribution  has  been  of  enormous  value  in  clarifying  our  thinking 
about  the  psychological  facts.  It  remained  to  correlate  the  distribu- 
tion of  energy  at  the  psychological  level  more  fully  with  the  energy 
systems  represented  by  the  bodily  organs.  The  organ  inferiority 
concept  took  the  first  step  in  this  direction. 

The  work  of  the  physiologists  (Cannon,  Crile)  and  the  neuro- 
physiologists  (Sherrington)  has  prepared  the  way  for  a  still  broader 
concept  of  the  relations  between  organic  states  and  their  psycho- 
logical repercussions  in  consciousness.  The  work  on  the  major 
emotions  (instincts)  such  as  fear,  anger,  and  hunger  has  shown  that 
in  the  case  of  fear,  for  instance,  there  are  definite  physiological 
conditions  incident  to  the  release  of  adrenalin  into  the  circulation 
which  produces  a  series  of  changes,  now  well  known,  which  register 
in  the  psyche  as  the  conscious  state  of  fear.  This  has  brought  about 
a  revivification  of  the  James-Lange  theory  of  the  peripheral  origin 
of  the  emotions  which  has  been  largely  utilized  (Kempf)  in  explaining 
the  organic  foundations  of  character.  The  primitive  emotions  cor- 
respond to  unsatisfied  instincts.  Hunger,  for  example,  is  the  instinct 
to  acquire  food  which,  when  neutralized,  ceases  to  exist,  but  when 
thwarted  is  a  mighty  motive  for  conduct  calculated  to  acquire  neu- 
tralizing stimuli  by  bringing  about  the  exposure  of  certain  receptors 
to  food.  It  is  these  organic  instincts  which  are  the  motive  forces  for 
conduct  and  the  interference  with  which,  their  repression,  is  regis- 
tered in  the  psyche  as  emotion,  which  can  be  further  conceived  as 
a  motor  set  of  the  organism  for  acquiring  certain  neutralizing  stimuli 
which,  however,  does  not  come  to  pass. 

It  is  but  logical  to  suppose,  and  the  facts  bear  out  the  supposi- 
tion, that  these  primitive,  phylogenetically  old,  archaic  reaction 
mechanisms  should  be  served  by  the  oldest  parts  of  the  nervous 


PSYCHIATRY   AND  GENERAL  MEDICINE      1233 

system,  namely,  the  autonomic  or  vegetative  nervous  system,  and 
that  the  motor  sets  should  be,  in  the  first  instance,  motor  sets  of 
the  older  variety  of  muscle,  the  smooth  or  involuntary  muscle.  The 
instincts  are  represented,  then,  by  the  autonomic  apparatus  which 
includes  (Kempf)  the  vegetative  nervous  system,  the  smooth  mus- 
culature, and  further  the  endocrine  glands  which  discharge  chemical 
stimuli  into  the  circulation — the  hormones — for  bringing  about  a 
correlation  at  this  level. 

Later  in  the  scheme  of  development  there  arises  the  phylo- 
genetically  very  much  younger  portion  of  the  nervous  system,  the 
cerebro-spinal  nervous  system,  consisting  largely  of  the  neuro- 
muscular apparatus  as  we  ordinarily  think  of  it,  that  is,  in  the  main, 
the  pyramidal  tract  system  and  the  voluntary  musculature.  This 
apparatus  is  calculated  to  bring  about,  with  far  greater  nicety,  the 
motor  responses  that  so  relate  the  organism  with  its  environment 
as  to  make  possible  the  securing  of  stimuli  which  will  neutraUze  the 
instinctive  cravings. 

The  distinguishing  features  of  this  more  recent  development  of 
the  nervous  system,  the  cerebro-spinal,  are  the  distance  receptors 
which  function  as  analyzers  of  the  environment  and  as  a  result  of 
such  analysis  condition  relatively  exact  responses  to  its  several 
characteristics. 

Recent  studies  have  indicated  (Langelaan,  Hunt)  that  in  the 
striped  muscle  we  have  a  double  system  of  innervation  which  so 
relates  the  autonomic  apparatus  and  the  cerebro-spinal  neuro- 
muscular apparatus — the  projicient  apparatus — as  to  insure  their 
working  in  harmony.  These  studies  tend  to  show  that  the  sarcoplas- 
matic  substance  of  striped  muscle  is  analogous,  if  not  identical, 
with  the  smooth  muscle  substance,  and  is  innervated  by  the  vege- 
tative nervous  system,  while  the  anisotropic  disk  system  is  the 
developmentally  more  recent  portion,  and  is  innervated  by  the 
cerebro-spinal  nervous  system.  It  can  thus  come  about  that  the 
motor  sets  of  the  autonomic  system  can  communicate  themselves 
to  the  voluntary  motor  apparatus. 

The  instincts  which  have  at  their  command  the  autonomic 
apparatus  and  its  interoceptors  bring  about  certain  motor  sets, 
which  are  expressed  in  various  forms  of  visceral  and  postural  tonus. 
Hunger  produces,  at  this  level,  the  periodic  contractions  of  the 


1234      PSYCHIATRY  AND   GENERAL  MEDICINE 

stomach  which  are  registered  in  the  psyche  as  a  desire  for  food  so 
long  as  they  continue.  The  projicient  apparatus,  with  the  aid  of  its 
exteroceptors,  can  initiate  motor  responses  calculated  to  expose  the 
stomach  receptors  to  neutralizing  stimuli — food — and  thus  cause 
the  craving  to  disappear. 

Psychology  has  advanced  beyond  the  purely  descriptive  stage  of 
development  in  which  it  devoted  its  energies  largely  to  the  analysis 
of  the  sensory  data  of  experience  and  was,  to  that  extent,  but  a 
refined  physiology  of  the  sense  organs.  It  has  now  become  a  study 
of  the  higher  aspects  of  energy  transformation  as  we  see  it  in  the 
human  individual.  The  great  motive  forces  of  conduct  lie  in  the 
instincts  and,  instead  of  seeing  sensation  as  the  unit  of  the  psyche, 
we  now  realize  that  it  is  the  registration  in  consciousness  of  the 
unsatisfied  instincts  which  constitute  that  unit,  namely  the  wish 
(Holt). 

From  the  point  of  view  of  the  integrated  organism  as  a  whole, 
its  tendencies,  the  nervous  pathways  may  be  considered  as  the  struc- 
turalized  precipitates  of  function.  That  is,  functions  which,  because 
they  have  been  sufficiently  often  repeated  and  because  it  is  essen- 
tial that  they  should  never  fail — like  the  relation  between  muscular 
exertion,  respiration,  and  cardiac  rate — come  to  be  laid  down  in 
structures  which  insure  certainty  and  definiteness  of  response. 
There  remains  an  unorganized  residuum  which  is  capable  of  reaction 
with  considerable  variation  to  unusual  and  infrequent  forms  of 
stimuli.  This  unorganized  residuum  is  represented  by  the  wish  at 
the  psychic  level  which  has  at  its  disposal  both  the  cerebro-spinal 
(sensorimotor)  and  the  autonomic  apparatus,  but  it  is  in  the  still 
imperfectly  organized  region  of  the  latter  that  the  machinery  for 
adjustment  to  the  unusual  is  contained.  Presumably  the  precipita- 
tion of  structuralized  pathways  is  still  going  on. 

This  approach  to  the  problems  of  the  individual  organism,  man, 
considers  it  as  a  receiver,  transformer,  and  distributor  of  energy 
in  which  the  action  patterns  are  in  part  laid  down  in  structure,  in 
part  represented  by  physiological  functions  that  take  the  form  of 
visceral  and  postural  tonicities.  The  head  end  of  the  principal, 
axial,  dynamic  gradient  is  the  locus  in  which  is  contained  the 
supreme  commander  of  the  various  mechanisms  and  structures  for 
translating  them  into  action. 


PSYCHIATRY  AND  GENERAL  MEDICINE      1235 

From  this  point  of  view  it  is  apparent  that  the  personality,  as  an 
energy  system,  can  no  longer  be  neglected  in  the  study  of  the  in- 
dividual, not  only  by  the  psychiatrist,  but  as  well  by  the  internist, 
if  all  the  factors  that  enter  into  a  given  problem  are  to  be  uncovered 
and  the  several  parts  they  play  adequately  evaluated.  Like  all  new 
concepts,  it  commends  itself  as  possibly  offering  explanations  for 
that  group  of  diseases,  and  those  aspects  of  disease  which  have,  up 
to  the  present  time,  defied  explanation. 

Certain  of  the  endocrinopathies  (particularly  thyroid  and 
adrenal)  at  once  suggest  this  angle  of  approach  as  offering  problems 
of  adjustment  which  have  as  yet  not  been  sufficiently  organized  to 
be  laid  down  in  structure.  Various  visceral  disorders  such  as  spasms 
(pylorospasm,  spastic  constipation)  suggest  a  similar  approach  in 
which  the  spasm  can  be  understood  as  confining  the  energy  of  an 
organic  craving  which  is  unable  to  gain  an  outlet  in  expression  by 
commanding  a  final,  common  motor  path.  This  is  the  physiological 
mechanism  at  the  basis  of  what  the  psychoanalysts  call  fixation 
and  repression.  Some  of  the  myopathies  invite  study  from  the  p>oint 
of  view  of  postural  tensions.  More  massive  phenomena  such  as 
epilepsy  and  catatonic  states  come  in  for  like  consideration,  while 
in  the  more  obvious  functional  types  of  cardiac  disorder,  the  con- 
versions of  hysteria  and  a  host  of  so-called  hysterical  symptoms,  the 
presence  of  a  psychogenic  factor  is  already  accepted.  More  clearly 
defined  disease  types  such  as  diabetes  suggest  further  study  along 
these  lines,  while  such  organic  conditions  as  chronic  nephritis,  pul- 
monary tuberculosis,  and  even  cancer  may  have  their  etiology  illu- 
minated by  a  closer  study  of  the  life  histories  of  those  in  whom 
they  develop,  with  a  view  to  discovering  the  dynamic  factors  which 
have  been  at  work  throughout  the  life  of  the  individual,  and,  oper- 
ating as  long-continued  stresses,  finally  broken  down  the  organic 
compensations  in  certain  directions. 

Just  as  these  disease  problems  can  be  advantageously  approached 
from  this  angle,  so  can  other  similar  problems  be  perhaps  illuminated 
in  the  same  way.  For  example,  the  problem  of  why  certain  etio- 
logical factors,  for  instance,  the  tubercle  bacillus,  should  attack  the 
lung  in  one  person,  the  kidney  in  another,  etc.  The  study,  for  ex- 
ample, of  the  relation  of  pulmonary  tuberculosis  to  the  shut-in 
type  of  character  and  the  dynamic  factor  back  of  this  character 


1236      PSYCHIATRY  AND  GENERAL   MEDICINE 

trait  which  may  well  be  of  more  importance  than  the  tubercle 
bacillus  itself,  because  primary,  because  offering  a  point  of  attack 
in  prophylaxis,  and  because,  unless  dealt  with,  making  a  cure  im- 
possible. It  has  been  in  the  past  usual  to  explain  such  problems  by 
heredity,  but  this  stamps  the  issue  as  final  and  irremedial  and 
sterilizes  effectually  all  therapeutic  effort. 

These  lines  of  research  suggest  that  the  question  which  should 
be  asked  of  the  disordered  human  machine  is.  What  is  the  individual 
trying  to  do?  This  question  recognizes  that  the  organism  is  an  in- 
tegrated whole  which  has  a  numerous  machinery  at  its  command 
for  bringing  to  pass  its  aims  which  are  registered  in  the  psyche  as 
desires,  wishes.  It  is  in  every  way  quite  as  appropriate  to  question 
the  human  organism  in  this  way  as  it  is  to  question  a  group  of  such 
organisms  in  that  integration  to  which  we  give  the  name  of  nation. 
We  have  a  right  to  ask,  for  example,  with  what  motives  the  several 
nations,  the  United  States,  England,  France,  Germany,  come  to 
the  peace  table.  Just  as  the  various  representations,  diplomatic 
moves,  dexterities  of  the  several  delegates  to  the  peace  conference 
can  only  be  adequately  understood  if  we  know  the  national  motives 
back  of  them,  so  the  various  disorders  of  function  of  the  several 
organs  of  the  individual  can  only  be  adequately  and  fully  understood 
when  they  are  appreciated  as  parts  of  the  complex  mosaic  of  the  indi- 
vidual, as  mechanisms  which  are  directed  to  the  larger  ends  of  the 
individual  as  a  whole. 

The  discussion  of  symptoms  might  be  prolonged  and  the  prin- 
ciples herein  set  forth  might  be  further  amplified,  particularly 
along  the  lines  of  their  application  to  the  interrelations  of  individuals 
in  the  social  milieu.  Suffice  it  to  rest  here  with  this  all  too  brief 
setting  forth  of  some  of  the  recent  trends  which  psychiatry  has 
either  evolved  or  taken  over  and  which  are  suggestive  of  a  time,  not 
far  distant,  when  the  personality  will  receive  its  due  meed  of  atten- 
tion in  the  study  of  the  sick  individual,  and  the  internist  and  the 
psychopathologist  will  work  hand  in  hand  because  of  an  apprecia- 
tion of  the  interdependence  of  their  several  problems  and  the  fact 
that  their  work  is  mutually  complementary. 

Psychiatry,  by  its  unremitting  emphasis  on  the  study  of  the  per- 
sonality make-up,  first  in  disease  and  later  as  necessary  in  order  to 
understand  the  symptoms  of  disease  when  they  do  develop,  has,  by 


PSYCHIATRY  AND  GENERAL  MEDICINE      1237 

finally  pressing  physiology  into  its  service,  eflfected  a  union  which  for 
the  first  time  really  begins  to  recognize  the  importance  of  considering 
the  individual  as  a  whole.  Internal  medicine  has  thought  that  it 
was  considering  the  individual  as  a  whole,  as  a  biological  unit,  when 
it  considered  all  of  the  organs  and  perhaps  the  most  obvious  of  the 
personality  traits.  The  study  of  the  personality,  from  the  two  op- 
posite angles,  the  psychological  and  the  physiological,  has  demon- 
strated the  inadequacy  of  this  assumption  and  indicated  quite 
clearly  that  between  these  two  lines  of  approach  much  more  is 
comprised  than  we  heretofore  suspected.  Psychiatry,  to  my  mind, 
is  the  first  medical  specialty  which  at  all  adequately  approaches 
the  problem  of  the  whole  individual,  and  I  may  say  that  that 
statement  epitomizes  its  contribution  to  general  medicine. 


THE  TOLERANCE  OF  FRESHLY  DELIVERED  WOMEN 
TO  EXCESSIVE  LOSS  OF  BLOOD 

By  J.  Whitridge  Williams,  M.D. 

Professor  of  Obstetrics,  Johns  Hopkins  University,  Baltimore,  Md. 

SOME  years  ago  I  became  impressed  with  the  fact  that  many 
women  may  lose  considerable  quantities  of  blood  during  the 
third  stage  of  labor  or  shortly  thereafter  without  presenting 
any  of  the  clinical  symptoms  which  are  generally  regarded  as  char- 
acteristic of  hemorrhage. 

In  order  to  test  the  correctness  of  my  impression,  I  instructed 
my  assistants  to  collect  and  measure  the  blood  lost  at  that  time  as  a 
matter  of  routine  in  every  labor.  As  the  number  of  observations 
increased  it  became  desirable  to  establish  a  standard  for  differen- 
tiating between  physiological  bleeding  and  actual  hemorrhage,  but 
upon  referring  to  the  standard  obstetrical  text  books  and  to  the 
monographs  upon  the  third  stage  of  labor,  I  was  surprised  by  the 
lack  of  definite  information  upon  the  subject,  as  well  as  by  the  con- 
tradictory statements  made  by  the  various  writers.  Thus,  in  1886 
Barnes  said: 

"  It  may  be  useful  to  acquire  as  accurate  an  idea  as  possible  of  what 
may  be  considered  the  natural  loss  of  blood.  This  standard  is  very  difficult 
to  fix  by  quantity.  Women  vary  greatly  in  this  respect.  Some  lose  very 
freely  without  appearing  to  be  any  the  worse;  whereas  others  cannot  bear 
the  loss  of  even  a  moderate  amount  without  exhibiting  alarming  pros- 
tration. When  the  uterus  contracts  normally,  its  substance  is  compressed, 
so  that  the  blood  in  its  vessels  is  squeezed  out,  much  as  we  squeeze  water 
out  of  a  sponge.  The  quantity  of  blood  so  held  in  the  uterus  at  the  moment 
of  separation  of  the  placenta  may  be  regarded  as  superfluous  quoad  the 
wants  of  the  system.  It  may  amount  to  i  pound,  but  it  is  often  less  and 
occasionally  more.  This  I  call  physiological  hemorrhage." 

While  Barnes's  statement  is  doubtless  correct,  it  is  nevertheless 
too  broad  to  be  useful  in  differentiating  or  indexing  hundreds  of 
observations.  Nor  are  the  estimates  of  other  writers  more  helpful, 
as  one  will  designate  as  normal  a  loss  of  blood  which  another  would 

1238 


BLOOD   LOSS  IN  FRESHLY  DELIVERED  WOMEN      1239 

consider  as  a  serious  hemorrhage.  The  following  figures  show  clearly 
the  varying  conceptions  of  physiological  bleeding:  Fabre,  80-100  c.c. 
Tucker,  300  c.c,  Champneys,  360  c.c,  G)mmandeur,  500  to  600  c.c, 
Tarnier  and  Chantreuil,  600  to  700  c.c,  and  Ahlfeld,  800  c.c;  while 
Polak  begs  the  question  by  stating  that  hemorrhage  did  not  occur 
in  a  series  of  1306  consecutive  labors.  It  must  be  apparent  that 
many  of  these  statements  represent  merely  crude  estimates;  for, 
so  far  as  I  can  gather,  only  the  figures  of  Tucker  and  Ahlfeld  are 
based  upon  actual  measurements.  Similar  variations  likewise  exist 
in  the  notions  as  to  what  constitutes  actual  hemorrhage,  its  lower 
limit  being  placed  at  300  and  1000  c.c  by  Fabre  and  Ahlfeld, 
respectively. 

The  present  study,  concerning  the  amount  of  blood  lost  during 
the  third  stage  of  labor  and  shortly  thereafter  and  its  clinical  efi'ects, 
is  based  upon  observations  made  upon  1000  consecutive  sp>ontaneous 
full-term  labors  occurring  in  1339  obstetrical  patients  at  the  Johns 
Hopkins  Hospital  (Histories  81 61-9500).  Of  these,  339  histories 
were  not  utilized,  as  they  included  162  operative  cases,  as  well  as 
177  others  in  which  pregnancy  had  terminated  prematurely,  or  in 
which  the  patients  left  the  hospital  before  delivery. 

Our  technic  for  collecting  and  measuring  the  blood  is  as  follows: 
Immediately  after  the  birth  of  the  child  a  sterile  douche  pan  is 
placed  beneath  the  buttocks  of  the  patient,  where  it  remains  until 
all  bleeding  following  the  birth  of  the  placenta  has  ceased.  After 
the  placenta  has  been  delivered  any  blood  contained  within  its 
membranes  is  allowed  to  escape  into  the  pan,  then  poured  into  a 
graduate,  accurately  measured  in  cubic  centimeters,  and  noted  in 
the  history.  In  this  way  contamination  by  amniotic  fluid  is  avoided, 
and  all  blood  which  has  escaped  during  the  third  stage  of  labor  and 
after  the  extrusion  of  the  placenta  is  collected  and  measured.  This 
technic  is  very  simple  and  is  preferable  to  that  employed  by  Tucker 
and  Ahlfeld — the  former  collecting  the  blood  in  a  basin  held  before 
the  external  genitaha,  and  the  latter  employing  a  complicated 
procedure  in  which  the  patient's  buttocks  rest  over  the  mouth  of  a 
large  copper  funnel,  which  passes  through  the  mattress,  the  blood 
being  collected  in  a  vessel  placed  beneath  the  bed. 

Before  considering  our  observations  in  detail,  it  seems  advisable 
to  say  a  few  words  concerning  the  conduct  of  the  placental  period 


1240     BLOOD  LOSS  IN  FRESHLY  DELIVERED  WOMEN 

of  labor,  as  our  method  differs  materially  from  that  employed  by 
Ahlfeld.  As  is  well  known,  he  advocates  the  greatest  possible  con- 
servatism, and  holds  that  it  results  in  a  diminution  in  the  amount 
of  blood  lost,  as  well  as  in  prompter  recovery  of  the  patient.  Im- 
mediately following  the  birth  of  the  child,  he  cuts  the  cord  and  leaves 
the  patient  absolutely  alone  for  two  hours,  unless  excessive  bleeding 
necessitates  prompt  expression,  or  the  placenta  is  extruded  spon- 
taneously, the  latter  occurring  in  only  13  per  cent  of  his  cases.  At 
the  end  of  the  period  he  expresses  the  placenta  by  gentle  pressure 
upon  the  lower  abdomen. 

I  have  adopted  a  different  procedure,  which  is  as  follows:  After 
the  child  is  born  the  uterus  is  gently  palpated  and  the  location  of 
its  fundus  noted,  but  massage  is  not  employed  unless  the  uterus 
is  boggy  in  consistency  or  the  bleeding  excessive.  From  time  to 
time  the  location  of  the  fundus  is  determined  by  palpation  or 
inspection,  and  after  the  lapse  of  from  five  to  thirty  minutes  it  is 
usually  noted  that  it  has  risen  4  to  6  cm.  above  its  original  location, 
while  in  some  cases  an  indistinct  swelling  has  likewise  appeared 
just  over  the  symphysis.  This  indicates  that  the  placenta  has  become 
separated  from  its  attachment,  has  been  extruded  from  the  uterine 
cavity,  and  lies  free  in  the  lower  uterine  segment  or  upper  part  of 
the  vagina.  As  Ahlfeld's  observations  have  taught  us  that  in  seven 
cases  out  of  eight  the  placenta  will  remain  in  this  location  until 
expressed  by  pressure  from  above,  I  have  been  unable  to  convince 
myself  that  there  is  any  advantage  in  waiting  a  specified  length  of 
time  before  expressing  it;  and  consequently,  as  soon  as  the  ris- 
ing of  the  fundus  indicates  that  it  has  been  extruded  from  the  uter- 
ine cavity,  I  express  it  from  the  vagina  by  gentle  pressure  upon 
the  fundus.  On  the  other  hand,  I  believe  that  routine  massage  of 
the  uterus  only  tends  to  disturb  and  prolong  the  process  of  separa- 
tion, and  should,  therefore,  be  avoided;  while  premature  attempts  to 
express  the  unseparated  placenta  by  the  original  Cred^  method 
frequently  lead  to  retention  of  placental  fragments  and  thus  greatly 
increase  the  amount  of  bleeding  and  the  frequency  of  radical  inter- 
vention. Q)nsequently,  I  employ  the  typical  Cred^  method  of  ex- 
pression with  the  greatest  circumspection,  and  only  in  the  presence 
of  serious  bleeding,  or  after  spontaneous  separation  of  the  placenta 
has  failed  to  occur  within  one  hour  after  the  birth  of  the  child. 


BLOOD  LOSS  IN  FRESHLY  DELIVERED  WOMEN      1241 

The  following  figures  give  a  clear  idea  of  our  conduct  of  the  third 
stage,  which  is  apparently  justified  by  the  results,  to  which  reference 
will  later  be  made. 

Cases 
Placenta  born  spontaneously g 

Placenta  expressed  from  vagina 973 

Placenta  expressed  by  typical  Cred6 18 

Placenta  removed  manually o 


1000 


In  the  entire  series,  the  average  time  elapsing  between  the  birth 
of  the  child  and  the  ex- 
trusion of  the  placenta 
was  15.3  minutes,  the  ex- 
tremes being  spontaneous 
expulsion  immediately 
following  the  birth  of  the 
child  and  a  difficult  Crede 
expression  at  the  end  of 
ninety  minutes. 

In  Chart  I  is  given  a 
graphic  representation  of 
the  duration  of  the  placen- 
tal period  in  our  series  of 
cases,  and  shows  that  the 
most  frequent  time  for  de- 
livery of  the  placenta  is 
between  ten  and  fifteen 
minutes  after  the  birth  of 
the  child,  or  somewhat 
less  than  the  arithmetic 
average. 

Upon  analyzing  the 
amount  of  blood  lost  in 
our  series  of  1000  spon- 
taneous labors,  we  find  that  the  average  bleeding  was  343.7  c.c, 
with  the  extremes  varying  from  zero  to  2400  c.c,  the  placental 
period  having  been  entirely  bloodless  in  two  patients.  Table  I  gives 
the  incidence  of  the  varying  loss  of  blood : 


MO 
ITS 
ISO 

vs 

[y 

V 

n 

^ 

ns 
/so 
OS 

no 

TS 
SO 

ts 

0 

1 

\ 

\ 

' 

1 

\ 

/ 

\ 

\_ 

V 

. 

( 

i 

M 

>  li 

\ » 

t  K 

(  M 

t  A 

f  « 

t  « 

(   S 

1  t. 

t  m 

1  « 

(  n 

t  » 

I  « 

t  1 

t 

Chart  I.  Showing  Duration  of  Placental 
Period  in  iooo  Consecutivk  Spontaneous 
Labors. 


1242      BLOOD  LOSS  IN  FRESHLY  DELIVERED  WOMEN 


TABLE  I 
Showing  the  Varying  Amount  of  Bleeding  in  1000  Spontaneous  Labors 


Quantity  of  Blood  Lost,  c.c. 

Cases 

0 

2 

1-     99 

88 

100-  199 

210 

200-  299 

227 

300-  399 

148 

400-  499 

120 

500-  599 

75 

600-  699 

31 

700-  799 

28 

800-  899 

15 

900-  999 

7 

1000-1099 

8 

1100-1199 

7 

1200-1299 

8 

1300-1399 

4 

1400-1499 

4 

1500-1749 

4 

1750-1999 

— 

2000-2249 

3 

2250-2499 

1 

Average  343 . 7  c.c. 

1000 

It  must  not  be  understood,  however,  that  this  average  loss  gives 
a  correct  idea  concerning  the  amount  of  bleeding  which  one  is  most 
likely  to  encounter  in  spontaneous  labor,  as  that  amounted  to  less 
than  300  c.c.  in  527  out  of  1000  cases.  This  is  still  further  accentuated 
by  Chart  II,  which  graphically  illustrates  the  conditions  in  our 
1000  cases,  and  shows  that  the  most  usual  loss  varies  between 
100  and  300  c.c,  and  that  the  higher  average  for  the  series  has 
resulted  from  the  inclusion  of  the  relatively  rare  cases  of  profuse 
hemorrhage. 

These  figures  correspond  approximately  with  those  of  Tucker 
and  Champneys  (300  to  360  c.c),  and  are  much  smaller  than  those 
given  by  Commandeur,  Tarnier  and  Chantreuil,  and  Ahlfeld 
(500-800  c.c).  In  the  last  2058  cases  studied  by  Ahlfeld  the  average 
loss  was  505.1  c.c,  which  is  16 1.4  c.c,  or  one-third,  greater  than  in 
our  series.  Whether  this  is  fairly  attributable  to  the  difference  in 
our  management  of  the  placental  period,  I  hesitate  to  state;  but  in 
any  event  it  can  scarcely  serve  as  an  argument  in  support  of  the 


BLOOD   LOSS  IN  FRESHLY  DELIVERED  WOMEN      1243 

view  that  extreme  conservatism  necessarily  leads  to  a  pronounced 
diminution  in  the  amount  of  bleeding. 

While  such  statistics  may  be  of  practical  value  to  the  obstetri- 
cian, they  are  of  little  interest  to  medical  men  in  general;  but,  on 
the  other  hand,  our  obser- 
vations as  to  the  incidence 
of  actual  hemorrhage,  and 
more  particularly  concern- 
ing the  tolerance  which 
freshly  delivered  women  ap- 
pear to  exhibit  to  it,  are 
of  general  significance. 
Upon  entirely  arbitrary 
grounds  I  selected  600  c.c. 
as  the  limit  between  physi- 
ological bleeding  and  post- 
partum hemorrhage,  and 
our  figures  show  that  130 
cases  in  the  series  (13 
per  cent)  belong  in  the 
latter  category.  Table  II 
shows  the  frequency  and 
amount  of  such  hemor- 
rhages : 


cttfMMo  urn 


VT-n 


Chart  II.  Showing  Amount  and  Fre- 
quency OF  Bleeding  Following  iooo  Consec- 
utive Spontaneous  Labors. 

TABLE  II 

Showing  Frequency  and  Amount  of  Post-partum  Hemorrhages  in  1000  Spon- 
taneous Labors 


Quantity  of  Blood  Lost,  c.c. 

Cases 

600 

130 

800 

71 

1000 

49 

1250 

18 

1500 

8 

2000 

4 

2400 

1 

As  experience  has  taught  me  that  in  normal  freshly  delivered 
women  serious  symptoms  do  not  follow  hemorrhages  of  less  than 
1000  c.c,  our  interest  is  centered  up>on  the  49  women  who  lost  one 
liter  or  more.  Of  these,  31  lost  between  1000  and  1250  c.c.  of  blood 


1244     BLOOD  LOSS  IN  FRESHLY  DELIVERED  WOMEN 

and  1 8  more  than  that  quantity.  As  only  one  patient  in  the  first 
group  presented  symptoms  of  acute  anemia,  we  are  particularly 
interested  in  the  i8  women  of  the  second  group,  abstracts  of  whose 
histories  are  given  at  the  end  of  the  article.  Of  these,  lo  lost  less  and 
8  more  than  1500  c.c.  of  blood,  the  latter  being  distributed  as 
follows: 

2  patients  lost  1500  c.c.  (Cases  XLII  and  XLIII) 
I  patient  lost  1600  c.c.  (Case  XLIV) 

1  patient   lost  1700  c.c.  (Case  XLV) 

2  patients  lost  2000  c.c.  (Cases  XLVI  and  XLVII) 
I  patient   lost  2100  c.c.  (Case  XLVIII) 

I  patient  lost  2400  c.c.  (Case  XLIX) 

While  49  hemorrhage  cases,  in  which  the  loss  of  blood  was  1000  c.c. 
or  more,  constitute  too  small  a  number  to  justify  the  formulation 
of  far-reaching  conclusions,  I  nevertheless  believe  that  their  study 
will  bring  out  several  points  of  interest  and  importance.  The  only 
other  study  of  the  kind  with  which  I  am  familiar  was  made  in  1904 
by  Ahlfeld,  who  reported  that  in  a  series  of  6000  labors,  post-par- 
tum  hemorrhages  amounting  to  1500  c.c.  or  more  occurred  in 
159  women,  an  incidence  of  2.65  per  cent  as  compared  with  our 
0.8  per  cent.  His  cases  were  divided  as  follows: 

132  patients  lost  1500-2000  c.c. 
23  patients  lost  2000-2500  c.c. 
4  patients  lost  2500  c.c.  or  more, 

with  4  deaths  in  the  first  group,  i  in  the  second,  and  none  in  the 
third.  Furthermore,  he  related  the  history  of  a  patient  not  included 
in  his  series  who  recovered  from  a  hemorrhage  of  3250  c.c.  without 
serious  symptoms. 

It  is  generally  believed  that  patients  suffering  from  serious 
hemorrhage  present  a  succession  of  more  or  less  characteristic  clinical 
symptoms,  the  most  important  of  which  are :  rapid  and  small  pulse, 
shock,  air  hunger,  and,  if  recovery  ensues,  a  rapid  decrease  in  the 
percentage  of  hemoglobin,  together  with  a  marked  diminution  in 
the  number  of  red  cells,  which  reaches  its  lowest  point  by  the  third 
day,  and  then  gradually  returns  to  normal.  The  histories  given 
below,  however,  conclusively  demonstrate  that  not  a  few  freshly 


BLOOD   LOSS  IN  FRESHLY  DELIVERED  WOMEN      1245 

delivered  women  may  lose  excessive  quantities  of  blood  without 
presenting  any  evidence  of  shock,  and  that  occasionally  the  extent 
of  the  hemorrhage  would  not  have  been  appreciated  had  the  blood 
lost  not  been  collected  and  measured.  Thus,  only  i  of  the  3 1  women 
who  lost  between  1000  and  1250  c.c.  presented  any  immediate 
symptoms  attributable  to  loss  of  blood,  but  she  was  considerably 
shocked,  and  had  a  pulse  rate  of  118  one  hour  and  a  quarter  after 
delivery  (Case  XXX).  Furthermore,  only  4  of  the  18  patients  losing 
from  1250  to  2400  c.c.  caused  us  any  anxiety;  none  was  seriously 
ill  and  all  recovered. 

It  is  currently  believed  that  the  pulse  is  unusually  slow  during 
the  normal  puerperium,  and  that  the  readiest  method  of  evaluating 
the  effect  of  hemorrhage  is  by  its  increased  rate  and  poor  quality. 
Our  observations,  however,  show  that  the  first  assumption  is  incor- 
rect, and  that  in  freshly  delivered  women  the  second  does  not  occur 
with  the  regularity  one  might  expect. 

In  going  over  our  1000  cases,  particular  attention  was  directed 
to  the  condition  of  the  pulse  during  the  forty-eight  hours  following 
delivery,  and,  as  it  was  counted  as  a  matter  of  routine  at  four-hour 
intervals,  we  usually  had  a  record  of  twelve  counts  for  the  period. 
The  highest  count  in  each  case  was  recorded  and  used  for  statistical 
study,  and  the  following  table  shows  that  most  of  the  women  at 
some  time  during  this  period  had  a  more  rapid  pulse  rate  than  is 
generally  believed. 

TABLE  III 

Showing  the  Highest  Pulse  Rate  during  the  First  Forty-eight  Hours  of  the 

Puerperium 


Pulse  Below 

Cases  without 
Hemorrhage 

Cases  with 
Hemorrhage 

Total 

60 

1 

— 

1 

60-  69 

15 

1 

16 

70-  79 

97 

7 

104 

80-  89 

273 

31 

304 

90-  99 

314 

44                                     358 

100-109 

112 

25 

137 

110-119 

36 

14 

50 

120-129             1 

17 

5 

22 

130  and  over 

7                                     1 

8 

872                                   128                 ! 

1000 

1246      BLOOD  LOSS  IN  FRESHLY  DELIVERED  WOMEN 


In  the  two  groups  the  average  rate  was  91.66  and  96.45  re- 
spectively, which  apparently  indicates  that  the  average  effect  of 
hemorrhage  is  to  raise  the  pulse  rate  by  only  five  beats.  Chart  III 
represents  these  figures  graphically,  and  clearly  shows  that  the  pulse 
rate  most  usually  encountered  is  between  80  and  100,  irrespective 

3^^ of  whether  labor  is  followed 

by  physiological  bleeding  or 
by  actual  hemorrhage. 

Furthermore,  it  is  in- 
teresting to  compare  these 
findings  with  those  observed 
in  the  operative  deliveries, 
which  were  interpolated 
between  the  1000  normal 
labors.  Of  the  162  opera- 
tions, 138  were  not  associ- 
ated with  hemorrhage,  and 
these  showed  an  average 
pulse  rate  of  10 1.9,  which  in 
turn  was  five  beats  higher 
than  that  observed  in  the 
spontaneous  labors  followed 
by  hemorrhage. 

From  a  study  of  these 
figures  it  seems  justifiable 
to  conclude:  (i)  That  the 
pulse  rate  following  normal 
spontaneous  labor  is  higher 
than  is  generally  believed; 
(2)  that  post-partum  hemorrhage  leads  to  a  slighter  relative 
elevation  than  would  be  anticipated  a  priori;  and  (3)  that  the 
strain  of  a  difficult  labor  which  necessitates  operative  termination 
results  in  a  greater  average  elevation  than  does  post-partum  hemor- 
rhage. 

Professor  Raymond  Pearl  was  kind  enough  to  study  these 
figures  from  a  statistical  point  of  view,  and  has  formulated  his 
data  in  Table  IV: 


so   eo    70   eo  so    100  no  120  130  140  /so. 
BEATS    PER  MINUTE 

Chart  III.  Showing  Highest  Pulse  Rate 

DURING  THE  FiRST  48  HoURS  FOLLOWING  DE- 
LIVERY IN  1000  Spontaneous  Labors.  Vertical 
AND  Oblique  Lining  Indicates  Cases  with  or 
without  Hemorrhage,  Respectively. 


BLOOD   LOSS  IN  FRESHLY  DELIVERED  WOMEN      1247 


TABLE  IV 
Pulse  Rate  in  Spontaneous  and  Operative  Labors 


Spontaneous  Labors 

Operative 
Labors 

Without 
Hemorrhage 

With 
Hemorrahge 

With 
Hemorrhage 

Average 

91-66±    -27 

1       96.45±    -75 

101 -89±    -91 

Standard  Deviation 

ll-90±      19 

1       12-61 ±    -53 

15-81±    -64 

Coefficient  of  variation 

12-98 ±     21 

1       13 -071    -56 

15-52±    -64 

Mode 

88.48±l-36 

1       93-08±l-30 

91-72  ±1  53 

Median 

91  09 

1       9518 

98-59 

Skewness 

+        •27±      11 

1+        •27±    -08 

+        -64±    -12 

from  which  he  has  drawn  the  following  conclusions: 

"i.  In  spontaneous  labors  the  average  pulse  rate  is  increased  only 
about  five  beats  in  the  cases  with  hemorrhage  as  compared  with  those  with- 
out. This  increase,  while  absolutely  small,  is  clearly  significant  statistically, 
having  regard  to  the  probable  errors.  In  operative  labors  the  rate  is  about 
ten  beats  higher,  without  hemorrhage. 

"2.  The  modal  pulse  rate  is  smaller  than  the  average  in  every  case; 
the  skewness  of  the  distribution  being  in  the  positive  direction. 

"3.  In  the  case  of  spontaneous  labors  the  skewness  is  not  certainly 
significant  in  comparison  with  its  probable  error." 

Passing  from  these  general  statistical  data  to  the  condition  of 
the  pulse  in  the  individual  cases  of  severe  hemorrhage,  I  find  it 
impossible  to  make  any  categorical  statement  concerning  it,  and  I 
can  only  say  that  in  many  cases  its  rate  and  character  during  or 
shortly  after  post-partum  hemorrhage  in  no  way  correspond  to  the 
quantity  of  blood  lost,  and,  therefore,  they  are  not  necessarily  in- 
dicative of  the  gravity  of  the  condition.  Table  V  gives  a  graphic 
idea  of  such  variations. 

From  these  figures  it  is  clearly  evident  that  in  certain  cases  the 
immediate  clinical  symptoms  were  not  proportionate  to  the  degree 
of  hemorrhage,  and  in  several  instances,  notably  in  Case  XLVIII, 
the  extent  of  hemorrhage  would  have  escaped  observation  had  the 
blood  lost  not  been  measured  as  a  routine  procedure.  Likewise,  in 
Case  XLIX,  the  pulse  rate  and  the  general  condition  of  the  patient 
gave  no  indication  that  2400  c.c.  of  blood  had  been  lost;  although 
the  fall  of  the  blood  pressure  to  70  immediately  after  its  cessation 
indicated  profound  shock,  and  the  decrease  in  the  hemoglobin  con- 


1248     BLOOD  LOSS  IN  FRESHLY  DELIVERED  WOMEN 

tent  to  38  per  cent  on  the  third  day  gave  conclusive  evidence  of  the 
existence  of  pronounced  anemia. 

TABLE  V 

Showing  Pulse  Rate  Immediately  after,  and  Hemoglobin  Percentage  Three 
Days  after  Post-partum  Hemorrhage 


Cases 

Amount 
Bleeding 

Pulse 

Hemoglobin 

Third  Day, 

Per  Cent 

Notes 

30 

1000  c.c. 

118 

? 

Definite  shock. 

42 

1500  c.c. 

136 

? 

Pulse  84  four  hours  later. 

43 

1500  c.c. 

90 

55 

No  immediate  symptoms. 

44 

1600  c.c. 

rapid 

42 

Pulse  75  four  hours  later. 

45 

1700  c.c. 

good 

? 

Pulse  65  four  hours  later. 

46 

2000  c.c. 

good 

38 

Pulse  104  one  and  a  half  hours  later 
(red  cells  fifth  day,  2,632,000). 

47 

2000  c.c. 

good 

42 

Pulse  78  three  hours  post-partum. 

48 

2100  c.c. 

84                  40           1   Pulse  104  one  hour  later. 

49 

2400  c.c. 

100 

38 

Pulse  115  one  and  a  half  hours  later 
(blood  pressure  70  immediately  after). 

Table  V  also  gives  information  concerning  the  hemoglobin 
content  of  the  blood  on  the  third  day,  and  makes  it  apparent  that 
in  five  of  the  severe  cases  a  pronounced  reduction  had  occurred. 
In  several  instances  a  rapid  return  to  normal  was  noted,  but  in 
others  the  low  percentage  persisted  throughout  the  patient's  stay 
in  the  hospital. 

Unfortunately,  routine  hemoglobin  examinations  were  not  made 
in  all  of  the  patients  losing  looo  c.c.  or  more  of  blood,  but,  as  far 
as  our  figures  go,  it  may  be  said  that  the  hemoglobin  content  was 
not  markedly  lowered  unless  the  hemorrhage  exceeded  1250  c.c, 
but  beyond  that  limit  several  marked  reductions  were  noted.  For 
example,  readings  of  40  per  cent  were  made  upon  two  patients  who 
lost  1350  and  1400  c.c.  respectively,  which  are  practically  identical 
with  those  noted  in  patients  losing  from  2000  to  2400  c.c. 

It  is  apparent  that  a  certain  proportion  of  freshly  delivered 
women  may  lose  from  1250  to  2400  c.c.  of  blood  with  comparative 
impunity,  and  present  such  slight  immediate  symptoms  that  the 
extent  of  hemorrhage  might  escape  recognition  if  the  blood  were 
not  collected  and  measured.  If  the  usual  computation  be  accepted, 
that  the  total  amount  of  blood  in  the  body  corresponds  to  1/13  of 
the  body  weight,  and  assuming  that  the  latter  averages  130  pounds, 
such  hemorrhages  mean  that  the  patients  had  lost  from  one-quarter 


BLOOD  LOSS  IN  FRESHLY  DELIVERED  WOMEN      1249 

to  one-half  of  their  total  blood.  In  males  and  non-pregnant  women 
such  a  loss  would  inevitably  be  followed  by  alarming  symptoms  of 
shock  and  acute  anemia,  yet  the  patients  here  mentioned  did  not 
so  suffer,  nor  was  their  general  condition  so  serious  that  the  necessity 
for  transfusion  was  at  any  time  entertained. 

The  question  accordingly  arises  as  to  how  such  an  immunity 
is  brought  about,  and  why  the  characteristic  symptoms  of  shock  do 
not  always  develop.  There  can  be  no  question  concerning  the  actu- 
ality of  the  hemorrhage,  as  its  amount  was  accurately  measured, 
and  furthermore,  the  striking  reduction  in  the  hemoglobin  content 
on  the  third  day,  as  well  as  the  marked  pallor  and  definitely  anemic 
appearance  of  some  of  the  patients,  aflfords  still  further  evidence  of  a 
serious  loss  of  blood.  Yet  in  many  cases  the  pulse  remained  good  in 
quality  and  was  scarcely  accelerated  in  rate. 

The  first  explanation  to  occur  to  one  is  that  so  decided  an  in- 
crease in  the  total  amount  of  blood  had  taken  place  during  the  latter 
months  of  pregnancy  that  the  amount  lost  by  hemorrhage  repre- 
sented a  smaller  proportion  of  the  total  content  in  pregnant  women 
than  would  have  been  the  case  in  non-pregnant  individuals,  with 
the  result  that  the  fraction  remaining  in  the  body  is  sufficient  to 
tide  over  the  immediate  needs.  A  certain  plausibility  is  lent  to  such 
an  explanation  by  the  observations  of  Miller,  Keith,  and  Rountree, 
made  in  my  service,  that  an  increase  in  the  total  amount  of  blood 
actually  occurs  during  pregnancy.  I  do  not  believe,  however,  that 
such  an  explanation  is  permissible,  for  two  reasons:  First,  because  the 
normal  increase  is  only  slight;  and  secondly,  that  the  low  hemoglobin 
content  noted  after  the  serious  hemorrhages  affords  indubitable 
evidence  that  a  large  proportion  of  the  blood  in  the  body  had  actu- 
ally been  lost. 

Some  other  explanation  for  the  relative  immunity  must,  there- 
fore, be  invoked;  but,  unfortunately,  we  are  not  in  a  position  to  do  so 
satisfactorily.  I  am  inclined,  however,  to  believe  that  it  is  in  some 
way  associated  with  other  protective  processes,  which  develop  dur- 
ing the  last  weeks  of  pregnancy  and  at  the  time  of  labor.  Slemons 
has  clearly  shown  that  the  nitrogenous  metabolism  at  the  time  of 
labor  is  reduced  to  a  minimum,  while  my  own  unpublished  obser- 
vations upon  the  respiratory  exchanges  indicate  that  the  parturient 
woman  can  go  through  labor  with  little  or  no  increase  in  energy 


1250      BLOOD  LOSS  IN  FRESHLY  DELIVERED  WOMEN 

consumption,  as  indicated  by  the  oxygen  intake  and  carbon  dioxide 
output.  In  other  words,  as  I  loosely  express  it  to  the  students,  she 
is  conducting  her  body  upon  a  "low  gear"  metaboHsm,  so  that  the 
amount  of  energy  necessary  for  the  demands  of  the  body  plus  the 
increased  work  incident  to  labor  is  scarcely  increased. 

If  this  supposition  is  correct,  it  may  be  permissible  to  assume  that 
the  temporary  immunity  to  excessive  loss  of  blood  may  in  some 
way  be  connected  with  such  a  mechanism,  and  that  the  relative 
absence  of  shock  may  be  due  to  the  fact  that  for  a  few  hours  after 
labor  the  patient  can  get  along  upon  a  greatly  diminished  amount 
of  blood,  so  that  by  the  time  the  normal  metabolism  has  been  re- 
estabhshed,  the  reparative  processes  will  be  sufficiently  well  under 
way  to  tide  the  woman  over  the  immediate  emergency.  It  must, 
however,  be  understood  that  such  an  explanation  is  entirely  theo- 
retical and  is  not  supported  by  any  known  facts. 

Finally,  in  order  to  avoid  any  possibility  of  misunderstanding, 
I  wish  to  emphasize  strongly  that  I  do  not  claim  that  freshly  de- 
livered women  are  entirely  immune  to  excessive  hemorrhage,  as  to 
do  so  would  be  running  contrary  to  ordinary  clinical  experience. 
But  what  I  wish  to  point  out  is  that  many  women  may  lose  large 
quantities  of  blood  with  apparent  impunity,  and  that  routine 
measurement  will  show  that  an  excessive  loss  occurs  much  more 
frequently  than  is  generally  believed.  In  my  experience  the  average 
normal  women  can  lose  1 250-1500  c.c.  of  blood  with  httle  or  no 
ill  effect;  and  many  can  lose  much  larger  quantities  with  rela- 
tive impunity.  At  the  same  time  a  recent  observation  in  private 
practice  has  taught  me  that  a  loss  of  1800  c.c.  may  put  the  life 
of  the  patient  in  the  greatest  jeopardy,  and  Ahlfeld  has  rep>orted 
several  fatalities  in  which  the  loss  barely  exceeded  1500  c.c. 

Abstract  oj  histories  of  patients  losing  1250  c.c.  or  more  blood  (including  one 
patient  presenting  symptoms  following  a  loss  of  only  looo  c.c). 

(In  Cases  I  to  XXIX,  the  loss  varied  from  1000  to  less  than  1250  c.c.) 
Case  XXX.  1000  c.c.  History  8210,  due  to  partial  seoaration  of 
placenta,  sixteen  years  old,  I  para.  Pelvis  normal,  L.  O.  P.  Prolonged 
second  stage.  Profuse  bleeding  immediately  following  birth  of  the  child 
necessitating  expression  by  Crede  in  four  minutes.  Patient  evidently 
shocked;  pulse  118  1V4  hours  post-partum. 


BLOOD  LOSS  IN  FRESHLY  DELIVERED  WOMEN      125 1 

Case  XXXI.  1250  c.c.  History  8300,  due  to  uterine  atony.  Twenty- 
three  years  old,  I  para.  Pelvis  normal,  L.  O.  A.,  labor  easy.  Bleeding 
after  expulsion  of  placenta  from  vagina.  No  note  as  to  symptoms.  Pulse 
104  two  hours  post-partum. 

Case  XXXII.  1250  c.c.  History  9286,  due  to  uterine  atony.  Twenty- 
three  years  old,  I  para.  Pelvis  normal,  R.O.A.  Pre-eclamptic  toxemia 
treated  for  three  weeks  before  labor.  Labor  prolonged,  second  stage  four 
hours  thirteen  minutes,  bleeding  entirely  after  expression  of  placenta 
from  vagina.  No  symptoms.  Pulse  84  three  hours  post-partum. 

Case  XXXIII.  1275  c.c.  History  8782,  due  to  uterine  atony.  Seventeen 
years  old,  I  para.  Pelvis  slightly  generally  contracted,  L.  O.  A,,  labor  easy. 
Bleeding  after  expulsion  of  placenta.  Condition  at  all  times  good.  Pulse 
75  1^/4  hours  post-partum. 

Case  XXXIV.  1300  c.c.  History  8491,  due  to  uterine  atony.  Twenty 
years  old,  I  para.  Pelvis  normal,  L.  O.  A.,  labor  prolonged,  second  stage 
three  hours.  Bleeding  after  expression  of  placenta  lasting  for  twenty 
minutes.  Although  the  patient  was  pale  for  two  days,  the  pulse  rose  only 
to  96  immediately  after  the  bleeding  and  soon  returned  to  normal. 

Case  XXXV.  1350  c.c.  History  8310,  due  to  partial  separation  of 
placenta.  Twenty  years  old,  I  para.  Pelvis  normal,  R.  O.  A.  Labor  easy, 
rep>eated  attempts  to  express  placenta  by  Cred6  were  not  successful  until 
one  hour  and  twenty  minutes  after  delivery.  During  the  entire  period 
bleeding  at  intervals,  which  ceased  completely  after  expression.  Con- 
dition good,  pulse  95  iVa  hours  post-partum. 

Case  XXXVI.  1350  c.c.  History  9492,  due  to  uterine  atony.  Twenty- 
four  years  old,  I  para.  Pelvis  normal,  L.  O.  A.,  labor  easy.  Bleeding  entirely 
after  expression  of  placenta,  uterus  boggy.  Patient  in  excellent  condition 
at  end.  Pulse  88  two  hours  p>ost-partum.  Hemoglobin:  second  day  $$ 
per  cent;  fourth  day  40  per  cent;  eighth  day  $$  per  cent. 

Case  XXXVII.  1375  c.c.  History  9494,  due  to  uterine  atony.  Twenty- 
two  years  old,  I  para.  Pelvis  normal,  L.  O.  A.,  labor  easy.  Bleeding  after 
completion  of  third  stage.  Patient  in  excellent  condition.  Pulse  104  two 
hours  post-partum.  Hemoglobin:  second  day  70  per  cent;  fourth  day  55  per 
cent;  tenth  day  65  per  cent. 

Case  XXXVIII.  1400  c.c.  History  8446,  due  to  uterine  atony.  Twenty- 
five  years  old,  I  para.  Pelvis  slightly  generally  contracted,  R.  O.  A.,  labor 
normal.  Bleeding  after  expression  of  placenta  from  vagina.  No  symptoms. 
Pulse  80.  Hemoglobin  on  fourth  day  $$  per  cent. 

Case  XXXIX.  1400  c.c.  History  8494,  due  to  uterine  atony.  Twenty- 
four  years  old,  I  para.  Pelvis  normal,  L.  O.  A.,  labor  easy,  bleeding  through- 
out the  third  stage,  but  particularly  after  expulsion  of  placenta.  Vigorous 


1252      BLOOD  LOSS  IN  FRESHLY  DELIVERED  WOMEN 

massage  necessary  for  one  hour  afterwards.  Pulse  90.  Hemoglobin:  $§,  40 
and  60  per  cent;  immediately  post-partum,  third  and  tenth  days  respec- 
tively. 

Case  XL.  1450  c.c.  History  9105,  due  to  partial  separation  and  atony. 
Seventeen  years  old,  I  para.  Pelvis  generally  contracted  rachitic.  L.  O.  T., 
labor  prolonged,  31^/4  hours.  Bleeding  began  immediately  after  the  birth 
of  the  child;  expression  by  Crede  eighteen  minutes  later.  Patient's  con- 
dition always  good.  Pulse  98  2V3  hours  post-partum;  iVa  hours  before 
birth  of  the  child  blood  pressure  was  124/94,  while  one  hour  after  the  birth 
of  the  child  it  had  fallen  to  98/74.  Hemoglobin:  iVa  hours  a.  p.  94.6; 
one  hour  p.  p.  89  per  cent;  third  day  67.3  per  cent;  tenth  day  90  per  cent. 

Case  XLI.  1475  c.c.  History  9073,  due  to  uterine  atony.  Eighteen  years 
old,  II  para.  Pelvis  normal.  L.  O.  A.,  labor  easy.  Bleeding  following  expres- 
sion of  placenta  from  vagina.  The  condition  was  never  alarming  and  the 
amount  of  bleeding  would  not  have  been  noted  had  the  blood  not  been 
measured.  Blood  pressure  on  admission  138/80;  after  conclusion  of  hemor- 
rhage 98/54.  Except  for  this  no  symptoms.  Hemoglobin:  end  of  second 
stage  82.6  per  cent;  one  hour  p.p.  81.4  per  cent;  third  day  54.5  per  cent; 
tenth  day  66.8  per  cent. 

Case  XLI  I.  1500  c.c.  History  8804,  due  to  partial  separation  of 
placenta  and  uterine  atony.  Eighteen  years  old,  I  para.  Pelvis  normal, 
L.  O.  A.,  labor  easy.  Bleeding  commenced  immediately  after  the  birth 
of  the  child,  necessitating  Crede's  method.  It  continued  afterwards  and 
gradually  ceased  after  the  hypodermic  administration  of  pituitrin.  Although 
the  pulse  rose  immediately  thereafter  to  136,  patient's  condition  was  never 
alarming;  pulse  fell  to  85  four  hours  later  and  did  not  exceed  104  after- 
wards. 

Case  XLIII.  1500  c.c.  History  8904,  due  to  partial  separation  of 
placenta.  Twenty-four  years  old,  I  para.  Pelvis  normal,  R.  O.  A.,  labor 
easy.  Oozing  throughout  entire  third  stage  ceasing  immediately  after- 
wards. No  symptoms.  Pulse  90.  Hemoglobin  immediately  p.p.  6$  per 
cent;  third  day  $$  per  cent  and  twelfth  day  60  per  cent. 

Case  XLIV.  1600  c.c.  History  8835,  due  to  uterine  atony.  Nineteen 
years  old,  II  para.  Pelvis  normal,  L.  O.  A.,  labor  easy.  Bleeding  after 
extrusion  of  placenta.  Immediately  thereafter  pulse  was  rapid,  but  never 
thready.  Four  hours  later  it  fell  to  75.  Hemoglobin  only  determined 
on  ninth  day,  when  it  was  42  per  cent. 

Case  XLV.  1700  c.c.  History  9356,  due  to  uterine  atony.  Thirty-nine 
years  old,  V  para.  Pelvis  normal,  R.  O.  P.,  prolonged  labor.  Hydramnios, 
3  liters.  Bleeding  after  completion  of  third  stage.  Retention  of  succenturiate 
lobe  was  suspected  but  was  not  found  on  introducing  hand  in  utero. 


BLOOD  LOSS  IN  FRESHLY  DELIVERED  WOMEN      1253 

Bleeding  stopped  after  a  hot  intra-uterine  douche.  Pulse  "good  quality," 
60  twelve  hours  p.p. 

Case  XLVI.  2000  c.c.  History  8268,  due  to  uterine  atony.  Twenty- 
three  years  old,  I  para.  Generally  contracted  funnel  pelvis.  L  O.  A.,  labor 
easy.  Bleeding  began  immediately  after  birth  of  the  child  and  as  it  con- 
tinued after  the  expulsion  of  the  placenta  the  cervix  was  examined  and 
found  not  to  be  torn,  whereupon  the  hand  was  introduced  into  the  uterus 
and  found  a  few  shreds  of  membranes  but  no  placental  tissue.  Hemorrhage 
controlled  by  intra-uterine  pack.  The  patient  was  not  sufficiently  shocked  to 
cause  a  special  note  to  be  made  in  the  history;  2Va  hours  later  pulse  104. 
Hemoglobin:  second  day  38  per  cent;  fifth  day  39  per  cent;  sixteenth  day 
38  per  cent;  the  number  of  red  cells  varying  from  3,120,000  to  2,632,000 
to  2,832,000  on  the  respective  days. 

G^SE  XLVI  I.  2000  c.c.  History  8393,  due  to  retained  fragments  of 
placenta.  Twenty-eight  years  old,  V  para.  Pelvis  normal,  R.  O.  P., 
labor  rapid.  Bleeding  following  expulsion  of  placenta  was  checked  only 
after  manual  removal  of  the  retained  fragments  followed  by  hot  intra-uterine 
douche.  Condition  at  no  time  alarming.  Pulse  78  three  hours  p.p.  Hemo- 
globin immediately  after  bleeding  60  per  cent;  first  day  42  per  cent;  elev- 
enth day  post-partum  42  per  cent. 

Case  XLVIII.  2100  c.c.  History  9265,  due  to  partial  separation 
of  placenta.  Twenty-nine  years  old.  III  para.  Pelvis  normal,  L  O.  P. 
Slightly  prolonged  labor.  Bleeding  began  ten  minutes  after  the  birth  of 
the  child  and  continued  until  the  placenta  was  expressed  from  the  vagina 
thirty  minutes  later.  During  this  entire  p>eriod  the  uterus  remained  firm 
and  the  loss  of  blood  would  not  have  been  noticed  had  it  not  been  col- 
lected and  measured.  No  treatment  required.  Pulse  of  good  quality  84, 
one  hour  later  104.  Hemoglobin:  twenty-four  hours  p.p.  40  p>er  cent; 
fourth  day  42  per  cent. 

Case  XLIX.  2400  c.c.  History  8941,  due  to  retention  of  placental  coty- 
ledon. Thirty-two  years  old,  I  para.  Pelvis  normal,  L.  O.  A.,  labor  easy 
and  rapid.  Bleeding  during  and  after  the  third  stage  necessitating  intro- 
duction of  the  hand  in  utero  and  the  removal  of  a  retained  cotyledon. 
Immediately  thereafter  the  pulse  was  100  and  the  blood  pressure  70; 
iVa  hours  later  the  pulse  had  risen  to  115,  where  it  remained  for  the  next 
twenty-four  hours.  Hemoglobin  immediately  post-partum  50  per  cent;  sec- 
ond day  38  per  cent;  and  tenth  day  60  per  cent. 


1254      BLOOD  LOSS   IN  FRESHLY  DELIVERED  WOMEN 

BIBLIOGRAPHY 

Ahlfeld,  "Die  Blutung  bei  der  Geburt  und  ihre  Folgen  fiir  die  Frau," 
Ztscbr.  J.  Geburtsb.  u.  Gyndk.,  1904,  LI,  341-364. 

Barnes,  " Post-partum  Hemorrhage."  "Lectures  on  Obstetrical  Opera- 
tions," IV  ed.,  1886,  440-465. 

Champneys,  "Mechanism  of  the  Third  Stage  of  Labor,"  II.  Tr.  Obst.  Soc., 
Lond.,  1887,  XXIX,  166. 

Commandeur,  "Perte  sanguine  apr^s  la  deliverance.  Bar,  Brindeau  et 
Chamberlent — La  pratique  de  Fart  des  accouchements,"   19 14,  I, 

453-455- 
Fabre,  "Precis  d'obstetrique,"  1910,  366. 
Miller,  Keith,  and  Rountree,  "Plasma  and  Blood  Volume  in  Pregnancy," 

J.  Am.  M.  Ass.,  1915,  LXV,  779-782. 
Polak,  "A  Study  of  the  Management  of  the  Placental  Stage  of  Labor," 

Surg.,  Gynec.  &  Obst.,  1915,  XXI,  590-593. 
Slemons,  "Metabolism  during  Pregnancy,  Labor,  and  the  Puerperium," 

Johns  Hopkins  Hosp.  Rep.,  1904,  XIII,  iii. 
Tarnier  et  Chantreuil,  "Traite  de  I'art  des  accouchements,"  1888,  I,  744. 
Tucker,  "Birth  of  the  Secundines,"  Am.  Gynaec.  &"  Obst.  J.,  1898,  XII, 

569-593.  767-794. 


INTRATRACHEAL  PULMONARY  IRRIGATION 
By  M.  C  Winternitz  and  G.  H.  Smith 

Department  of  Pathology  and  Bacteriology,  Yale  University,  School  of  Medicine,  New 

Haven,  Conn. 

THE  Studies  which  are  to  be  included  in  this  report  were  incited 
primarily  by  the  hope  that  the  intratracheal  route  might  be 
utilized  in  the  more  direct  application  of  therap>eutic  agents 
in  pulmonary  inflammatory  conditions.  While  the  main  objective 
has  not  been  attained,  the  preliminary  experiments  have  been  ex- 
tensive and  have  yielded  results  which  in  themselves  seem  worthy 
of  record. 

Contrary  to  general  opinion,  the  lungs  are  by  no  means  as  sus- 
ceptible to  the  introduction  of  foreign  material  as  is  generally  as- 
sumed. Huge  quantities  of  fluid  can  be  introduced  through  the  tra- 
chea without  any  untoward  results.  This  has  led  to  the  analysis  of 
the  role  that  fluid  within  the  pulmonary  alveoli  may  play,  and  it  is 
evident,  firstly,  that  the  significance  of  pulmonary  edema  as  a  cause 
of  death  is  challenged,  and  secondly,  that  in  acute  inflammatory 
processes,  fluid  in  the  pulmonary  parenchyma  may  be  a  means  of 
disseminating  the  infection  through  the  lung  tissue.  These  prelimi- 
nary studies  will  be  rep)orted  in  the  order  indicated  above,  and  will 
then  be  followed  by  a  discussion  of  the  possible  utility  of  the  intra- 
tracheal route  in  the  application  of  therapeutic  agents  to  pulmonary 
lesions. 

Material  and  Method.  All  of  the  experimental  work  has  been  done 
upon  normal  dogs,  and  the  material  has  been  brought  into  the  lungs  by  the 
usual  method  of  intratracheal  insufflation.  The  technic  is  very  simple  and 
involves  no  complicated  apparatus.  A  rubber  tube  of  about  8  ram.  in 
diameter,  and  with  a  heavy  wall  which  provides  the  desired  rigidity,  b 
passed  into  a  glass  tube  with  a  lumen  slightly  larger  than  the  diameter 
of  the  rubber  cannula.  It  is  necessary  to  have  the  glass  tubing  of  heavy 
wall  to  avoid  the  danger  of  breakage,  and  it  can  be  most  conveniently  ma^ 
nipulated  if  it  is  about  20  to  24  cm.  in  length.  After  sterilization  the  gUft 

1255 


1256         INTRATRACHEAL  PULMONARY  IRRIGATION 

tube  is  introduced  through  the  mouth  of  the  animal  until  its  end  is  within 
the  opening  of  the  trachea.  During  this  manipulation  the  rubber  cannula 
is  withdrawn  about  2  cm.  from  the  end  of  the  glass  tube,  so  that  it  does  not 
come  into  contact  with  the  saliva  and  thus  become  contaminated.  Very- 
gentle  pressure  exerted  upon  the  rubber  tubing  that  projects  from  the 
proximal  end  of  the  glass  protecting  tube  is  sufficient  to  force  the  rubber 
cannula  down  through  the  trachea.  The  glass  tube  thus  serves  two  purposes 
— it  avoids  the  necessity  of  directing  the  cannula  into  the  trachea  with 
the  hand,  which  obscures  the  vision,  and  it  also  permits  the  passage  of 
the  cannula  into  the  trachea  without  danger  of  contamination.  That 
the  cannula  is  in  the  trachea  can  be  readily  determined,  for  after  it  has  been 
passed  in  for  a  certain  distance,  that  is,  as  far  as  the  bifurcation,  its  path 
becomes  obstructed.  This  is  not  the  case  when  it  is  entering  the  stomach. 
Such  manipulation  can  be  done  much  more  readily  if  the  animal  is  thor- 
oughly anesthetized. 

For  the  introduction  of  fluid  two  methods  have  been  employed,  the 
method  of  choice  depending  largely  upon  the  amount  of  fluid  to  be  intro- 
duced. With  amounts  up  to  50  c.c,  satisfactory  results  have  been  secured 
by  simply  connecting  the  pipette  containing  the  fluid  with  the  projecting 
end  of  the  cannula,  and  forcing  the  fluid  in  by  means  of  a  compression  bulb 
attached  to  the  other  end  of  the  pipette.  With  such  small  amounts,  where 
it  is  essential  that  the  material  be  introduced  quantitatively,  this  method 
has  invariably  been  employed,  for  if  air  is  forced  through  the  cannula 
after  the  introduction  of  the  fluid,  there  is  no  danger  of  loss.  With  larger 
amounts,  where  a  slight  loss  does  not  cause  an  appreciable  error  or  where 
the  material  is  to  be  introduced  for  a  long  time,  the  gravity  method  has 
been  used.  In  such  a  case  the  cannula  is  connected  by  rubber  or  glass 
tubing  with  an  elevated  reservoir,  from  which  the  flow  of  fluid  is  regulated 
by  a  pinch-cock. 

Tolerance  oj  the  Lung  Jor  Fluid  Introduced  through  the  Trachea. 
Although  studies  on  the  production  of  pneumonia  by  intratra- 
cheal insufflation,  which  have  been  carried  on  so  extensively  in  the 
past  ten  years,  indicate  that  a  considerable  quantity  of  material 
may  be  introduced  into  the  pulmonary  parenchyma  by  this  route, 
recent  experiments  by  WoIIstein  and  Meltzer  (i)  indicate  that  in  one 
animal  at  least  (a  dog),  death  resulted  after  the  introduction  of  60 
c.c.  of  fluid,  and  in  the  opinion  of  the  authors  it  was  brought  about 
by  drowning.  This  result  is  quite  contrary  to  the  experiences  to  be 
quoted  below. 


INTRATRACHEAL  PULMONARY  IRRIGATION         1257 

A  series  of  experiments  was  undertaken  with  the  intention  of 
determining  how  much  fluid  can  be  introduced  into  the  lung  through 
the  trachea  with  safety.  Salt  solution  was  insufflated  in  definite 
amounts  per  kilogram  of  body  weight.  Five  cubic  centimeters  were 
readily  tolerated  and  the  quantity  was  increased  to  20  c.c.  per  kilo- 
gram of  body  weight.  At  this  point  it  became  evident  that  20  c.c. 
approached  the  limit  that  could  be  introduced,  not  because  of  any 
evident  harmful  eff"ect  upon  the  animal,  but  simply  because  the  ca- 
pacity of  the  lungs  had  been  reached.  When  30  c.c.  per  kilogram  of 
body  weight  was  attempted,  before  the  amount  was  completely 
introduced  there  was  a  flow  of  fluid  back  through  the  trachea  and 
mouth.  In  fact,  not  in  every  case  could  20  c.c.  per  kilogram  be  in- 
troduced without  refluence  of  some  of  the  salt  solution.  It  should 
be  noted  that  20  c.c.  of  salt  solution  per  kilogram  of  body  weight  in 
the  animals  which  were  utilized  amounted  to  between  200  and  450 
c.c.  in  total  volume. 

The  protocol  given  herewith  is  that  for  dog  Pn-37,  the  animal 
mentioned  above  as  having  received  an  insufflation  of  30  c.c.  per 
kilogram  of  body  weight.  It  is  typical  of  the  animals  of  this  series. 

Pn-37.  April  9,  1918,  4:25  P.M.  Intratracheal  insufflation  of  393  cc. 
of  physiological  salt  solution  (30  c.c.  per  kilogram).  After  about  275  c.c. 
had  been  introduced  the  excess  was  expelled.  The  dog  was  removed  from 
table  immediately  and  allowed  to  recover  from  the  anesthesia.  During  thb 
time  some  of  the  fluid  escaped  from  the  mouth.  There  was  no  manifest 
distress  aside  from  an  occasional  cough. 

April  10,  19 1 8.  The  dog  appeared  perfectly  normal  and  was  killed  with 
chloroform.  Some  fluid  not  yet  absorbed  remained  in  the  lung.  The  surface 
of  the  lower  right  lobe  was  somewhat  mottled  and  brownish  red.  The  other 
lobes  appeared  normal.  On  section  the  lungs  showed  nothing  abnormal. 

Microscopicafly:  There  was  slight  hemorrhage  into  the  bronchi,  with 
an  occasional  polymorphonuclear  leucocyte  and  slight  mechanical  dis- 
turbance of  the  alveoli  as  evidenced  by  their  variation  in  size.  There  was  no 
evidence  of  fluid  or  extensive  damage.  The  presence  of  polymorphonuclear 
cells  within  the  alveolar  walls  and  a  few  in  the  lumen  of  the  alveolus 
showed  that  there  had  been  a  slight,  but  definite,  inflammatory  reaction. 

This  protocol,  which  is  typical  of  a  large  series,  indicated  beyond 
peradventure  that  the  lung  will  tolerate  its  capacity  of  fluid  intro- 


1258         INTRATRACHEAL  PULMONARY  IRRIGATION 

duced  by  the  intratracheal  route,  and  that  under  the  conditions  of 
the  experiment  there  is  absolutely  no  danger  of  "drowning"  the 
animal. 

The  question  now  arises  whether  the  fluid  actually  enters  the 
alveoli  of  the  lung,  or  whether  it  simply  runs  into  the  ramifications 
of  the  tracheal  tree  and  becomes  refluent  before  the  alveoli  are 
reached.  It  is  quite  obvious  that  the  amount  of  fluid  that  can  be 
introduced  (200  to  400  c.c.)  could  not  be  confined  to  the  trachea 
and  bronchi,  but  in  order  to  make  the  evidence  absolute,  the  last 
portion  of  fluid  injected,  perhaps  25  c.c,  was  stained  with  India 
ink  and  the  animal  immediately  sacrificed.  The  ink  penetrated  and 
not  only  stained  the  lower  lobes  of  the  lung  throughout,  but  it  was 
found  in  widely  distributed  patches  in  the  upper  lobes.  None  of 
the  lobes  was  free  from  the  discoloration. 

These  experiments  indicate  clearly  that  fluid  introduced  into  the 
trachea  will  find  its  way  into  the  alveoli  themselves  and  that  the 
pulmonary  parenchyma  can  be  filled  to  capacity  with  normal  salt 
solution  without  provoking  any  untoward  symptoms  in  the  subject 
of  the  experiment. 

Absorption  from  the  Lung.  It  becomes  necessary  now  to  deter- 
mine the  fate  of  the  fluid  which  is  left  in  the  lung  following  the 
insufflation.  The  absorptive  powers  of  the  lung  have  not  been  de- 
termined to  any  extent,  but  it  has  always  been  believed  that  the 
very  extensive  blood  and  lymph  vascular  supply  in  this  tissue  can 
care  for  a  relatively  large  amount  of  material.  That  this  is  true  is 
quite  evident  from  experiments  in  which  phenolsulphonephthalein 
was  utilized  as  an  indicator.  In  the  same  subject  the  excretion  of  this 
dye  by  the  kidneys  was  determined  after  intravenous,  intramuscular, 
and  intrapulmonary  injections.  Of  course,  a  definite  period  was  al- 
lowed to  elapse  between  the  determinations  of  the  excretion  of  the 
drug  after  its  introduction  by  the  diff"erent  routes. 

The  amount  of  the  phenolsulphonephthalein  introduced  has  always 
been  the  same,  6  mg.,  although  in  the  case  of  the  intratracheal  insufflations 
this  quantity  was  contained  in  15  c.c.  The  volume  of  the  intramuscular  and 
intravenous  injections  was  i  c.c.  The  elimination  was  measured  in  dogs 
anesthetized  with  ether.  Before  the  injection  of  the  drug  the  dogs  were 
given  250  c.c.  of  water  by  stomach  and  a  catheter  was  passed  into  the 
bladder.  After  the  injection  or  insufflation  of  the  phenolsulphonephthalein 


INTRATRACHEAL  PULMONARY  IRRIGATION         1259 

solution  the  contents  of  the  bladder  were  removed  and  tested  every  five 
minutes  until  excretion  of  the  drug  was  detected. 

In  addition  to  the  tests  for  the  time  of  apF>earance  of  the  phthalein, 
the  urinary  excretion  for  half-hourly  periods  was  collected  separately,  the 
bladder  being  washed  out  at  the  end  of  every  such  j>eriod,  and  each  speci- 
men was  tested  for  its  phthalein  content.  Such  collections  were  made  up 
to  two  hours  after  the  introduction  of  the  drug. 

Pn-87.  June  28,  19 1 8.  250  c.c.  water  into  stomach  at  10.39  a.m.;  6  mg. 
phthalein  (in  15  c.c.)  into  lung  at  10.42  a.m.  The  drug  first  app>eared  in  the 
urine  at  10.55  a.m.  (thirteen  minutes).  Urine  excreted  collected  in  half- 
hourly  periods. 

Titrations:  Per  Cent 

First  half  hour 12.5 

Second  half  hour 20 .  o 

Third  half  hour 16.6 

Fourth  half  hour 8.0 


(a  hours)  57.1 

July  15,  191 8.  250  c.c.  water  into  stomach  at  2.37  p.m.;  6  mg.  phthalein 
injected  intramuscularly  at  2.39  p.m.  The  drug  first  appeared  in  the  urine 
at  2.54  P.M.  (fifteen  minutes).  Urine  excreted  collected  in  half-hourly 
periods. 

Titrations:  Per  Cent 

First  half  hour $-$ 

Second  half  hour 26.0 

Third  half  hour 170 

Fourth  half  hour ^o 


(a  hours)  72.5 

July  16,  1918.  250  c.c.  water  into  stomach  at  9.58  a.m.;  6  mg.  phthalein 
into  jugular  vein  at  10.17  a.m.  First  appearance  of  the  drug  at  10.22  a.m. 
(five  minutes).  Urine  collected  at  half-hourly  periods. 

Titrations:  P"  Cent 

First  half  hour ^4.0 

Second  half  hour 36.4 

Third  half  hour io-5 

Fourth  half  hour 7.*5 

(a  hours)  78.15 


iiCo 


INTRATRACHEAL  PULMONARY  IRRIGATION 


A  tabulation  of  these  results,  arranging  the  values  in  parallel  series, 
shows: 


1         Intrapulmonar 

1  Intramuscular  | 

Intravenous 

First  positive 

1                    13  min. 

15  min.          | 

5  min. 

First  half  hour 

1                    12-5% 

5-5%           1 

24.0% 

Second  half  hour 

1                    20-0 

26-0                1 

36-4 

Third  half  hour 

1                    16-6 

17-0                1 

10-5 

Fourth  half  hour 

1                      8-0 

24.0                1 

7-2 

Totals 

1                   57-1 

72-5               1 

781 

This  experiment,  valuable  as  it  may  be  to  indicate  the  absorption 
of  a  small  amount  of  fluid  through  the  tissues  of  the  lung,  does  not 
give  any  indication  of  the  rapidity  of  the  absorption  and  restitution 
to  normal  of  the  pulmonary  parenchyma  when  it  is  filled  to  capacity. 
To  arrive  at  some  conclusion  in  this  association,  a  series  of  experi- 
ments were  conducted  in  which  the  animals  were  sacrificed  at  vary- 
ing intervals  after  the  pulmonary  insufflation  to  determine  the 
residual  fluid  in  the  lung  tissue. 

Dogs  Pn-50  to  Pn-55  were  each  given  20  c.c.  of  salt  solution  per 
kilogram  of  body  weight.  After  varying  intervals  they  were  killed 
and  the  lungs  were  examined.  As  before,  no  disturbance  was  noted 
in  the  general  condition  of  the  animals  immediately  after  the  in- 
sufflation or  during  the  period  of  observation.  The  protocols  for  some 
of  these  dogs  follow. 

Pn-50.  Received  220  c.c.  or  salt  solution  and  was  killed  within  five 
minutes  of  the  completion  of  the  insufflation.  The  lungs,  aside  from  a  small 
portion  of  the  margin  of  the  upper  lobes,  were  found  to  be  completely  filled 
and  distended  with  fluid.  In  fact,  it  is  difficult  to  fill  the  lungs  to  such  an 
extent  that  the  upper  lobes  will  not  be  air-containing  in  some  p)ortions. 
The  lungs  were  normal  in  appearance  except  for  their  distention. 

Microscopically:  There  was  congestion  of  the  blood  vessels  and  an  oc- 
casional desquamated  epithelial  ceff  and  polymorphonuclear  leucocyte  in 
the  alveoli. 

Pn-52.  Received  180  c.c.  of  salt  solution  and  was  killed  after  fifteen 
minutes.  The  lungs  were  similar,  both  grossly  and  microscopically,  to  those 
of  dog  Pn-50. 

Pn-51.  Received  200  c.c.  of  salt  solution  and  was  killed  after  eighteen 
hours.  Much  of  the  fluid  had  been  absorbed,  although  there  was  a  con- 
siderable amount  in  the  lower  lobes. 

Microscopicafly:  The  picture  was  practically  identical  with  that  pre- 
sented by  Pn-50. 


INTRATRACHEAL  PULMONARY  IRRIGATION         1261 

Pn-53  and  Pn-54.  These  dogs  received  220  and  210  c.c.  respectively. 
Both  were  killed  after  four  days.  During  the  interval  they  appeared  to  be 
perfectly  well.  At  autopsy  the  lungs  were  found  to  be  practically  normal, 
with  but  little  fluid  remaining.  The  only  gross  change  was  the  presence  of 
a  few  pin-point  hemorrhagic  areas  scattered  over  the  surface  of  the  lower 
lobes. 

Microscopically:  Some  of  the  bronchi  contained  a  little  mucus  with  a 
few  red  blood  cells  and  an  occasional  polymorphonuclear  leucocyte.  The 
picture  suggested  desquamation  of  the  bronchial  epithelium.  There  was 
very  little  inflammatory  reaction. 

Pn-55.  Received  205  c.c.  of  salt  solution.  The  dog  remained  apparently 
normal  for  ten  days,  at  which  time  it  was  killed  for  examination.  The  lungs 
appeared  normal,  presenting  no  gross  lesions.  There  was  no  fluid  remaining 
in  any  of  the  lobes.  Microscopically,  the  tissue  appeared  normal. 

The  above  experiments  indicate  that  a  considerable  period  of 
time  may  be  necessary  before  fluid  introduced  into  the  alveoli  of 
the  lung  is  entirely  absorbed.  After  eighteen  hours  much  has  dis- 
appeared and  within  four  days  it  has  been  absorbed  without  a  trace. 
In  the  interim,  however,  and  for  several  hours  after  the  insufflation, 
if  the  animal  is  sacrificed  a  degree  of  artificial  edema  may  be  en- 
countered which  is  frequently  greater  than  that  met  with  when 
death  is  ascribed  to  this  condition.  This  has  led  to  a  consideration 
of  pulmonary  edema  as  a  cause  of  death. 

Pulmonary  Edema  as  a  Cause  of  Death.  During  the  past  two  years, 
while  the  studies  on  the  eff'ect  of  pulmonary  irritating  gases  (a) 
have  been  in  progress  in  this  laboratory,  particular  attention  has 
been  paid  to  the  very  striking  phenomenon  of  pulmonary  edema 
in  the  gassed  subject.  The  result  of  these  investigations  may  be 
briefly  summarized  in  the  following  paragraphs  (3). 

Animals  which  die  acutely  from  exposure  to  any  of  the  gases  of 
the  respiratory  irritant  group,  such  as  chlorine  and  phosgene,  show 
at  autopsy  varying  degrees  of  edema  of  the  lungs.  Although  this  is 
regularly  well  marked  in  certain  species,  dogs,  for  example,  there  arc 
wide  individual  variations.  In  other  species,  rats  and  guinea  pigs, 
for  example,  it  may  be  a  relatively  inconspicuous  feature  in  spite 
of  the  fact  that  these  animals  are  particularly  susceptible  to  effect  of 
the  gas. 

Dogs  which  have  been  killed  before  the  action  of  the  gas  reaches 
its  maximum  eff"ect  likewise  show  striking  diflferences  in  the  amount 


1262         INTRATRACHEAL  PULMONARY  IRRIGATION 

of  fluid  in  the  lungs,  and  these  diff"erences  do  not  harmonize  with  the 
variations  in  the  symptoms  manifested  by  the  animals.  Furthermore, 
many  dogs  which  pass  successfully  the  critical  forty-eight  hour 
period  and  are  classed  as  "recovered "often  show,  when  killed, edema 
of  the  lungs  of  greater  degree  than  other  dogs  of  the  same  experiment 
which  succumbed. 

These  observations,  together  with  the  results  of  the  experiments 
previously  quoted,  upon  what  may  be  termed  artificial  pulmonary 
edema  produced  by  filling  the  lungs  of  a  normal  dog  with  isotonic 
salt  solution,  have  led  to  the  conclusion  that  edema  of  the  lungs 
in  general  is  merely  an  indicator  of  some  underlying  disorder,  and 
is  not  directly  responsible  for  the  death  of  the  patient  or  animal. 

Pulmonary  Irrigation.  It  will  be  recalled  that  the  primary  object 
of  this  investigation  was  to  determine  whether  therapeutic  agents 
could  be  applied  directly  by  the  intratracheal  route  to  pulmonary 
lesions.  It  has  been  shown  not  only  that  the  lung  tissue  is  not  sus- 
ceptible, as  is  generally  believed,  to  the  introduction  of  foreign  ma- 
terial through  the  trachea,  but  that  large  quantities  of  isotonic  salt 
solution  can  be  introduced  without  any  harmful  eff"ects.  In  fact, 
artificial  edema  can  be  produced  which  exceeds  the  grade  which  is 
frequently  found  where  death  is  attributed  to  this  phenomenon,  and 
still  the  animal  shows  no  untoward  symptoms.  The  question  now 
arises  in  what  way  these  facts  can  be  utilized  for  the  elaboration  of 
the  primary  object.  It  is  at  once  obvious  that  there  are  two  separate 
modes  of  attack:  the  first,  irrigation  of  the  lung  tissue  through  the 
intratracheal  route,  and  the  second,  direct  application  of  specific  or 
non-specific  chemical  or  biological  agents. 

The  first  of  these  methods  has  been  more  completely  investi- 
gated, since  it  seemed  possible  that  it  could  be  utilized  successfully 
in  animals  during  the  very  acute  period  after  exposure  to  pulmonary 
irritating  gases.  These  poisons  act  upon  the  respiratory  epithelium 
in  such  a  way  as  to  incapacitate  more  or  less  completely  the  pro- 
tective mechanism  of  the  upper  respiratory  tract,  and  allow,  as  a 
consequence,  an  invasion  into  the  lung  of  the  bacteria  from  the 
mouth  or  from  the  inspired  air  (4).  The  initial  damage  to  the  lung 
already  present  when  the  organisms  reach  it  makes  this  a  favorable 
medium  for  bacterial  growth.  Naturally,  if  the  necrotic  material 
with  the  bacteria  could  be  washed  out,  beneficial  results  might  be 


INTRATRACHEAL  PULMONARY  IRRIGATION  1263 

expected,  and  for  this  reason  attention  was  concentrated  upon  an 
efficient  method  of  intratracheal  irrigation. 

The  procedure  does  not  differ  in  any  essential  way  from  that 
described  for  pulmonary  insufflation  except  that  much  larger 
quantities  of  fluid  have  been  used.  The  irrigation  has  been  conducted 
either  as  a  continuous  or  intermittent  process,  with  the  fluid  always 
introduced  by  the  gravity  method.  In  the  intermittent  method  the 
lungs  are  entirely  flooded  with  the  salt  solution,  and  then  the  flow 
from  the  reservoir  is  cut  off  for  a  few  minutes,  during  which  time  the 
lungs  are  allowed  to  drain.  When  the  salt  solution  ceases  to  flow 
from  the  trachea  and  mouth,  the  lungs  are  again  flooded,  and  this 
process  is  repeated  throughout  the  application  of  the  perfusion.  With 
the  continuous  method  of  perfusion,  the  force  of  the  flow  from  the 
reservoir  is  cut  down  and  a  small  stream  of  fluid  is  allowed  to  enter 
into  the  lungs  throughout  the  experiment.  The  intermittent  method 
has  given  more  satisfactory  results.  It  is  better  tolerated  by  the 
animal  and  there  is  no  serious  interference  with  the  respiration. 
With  the  completion  of  irrigation,  recovery  from  the  anesthesia 
occurs  somewhat  slowly,  but  in  a  short  time  the  animal  app>ears 
normal.  The  period  of  irrigation  has  frequently  exceeded  three  hours 
and  as  much  as  6000  c.c.  of  fluid  have  been  allowed  to  pass  through 
the  lungs.  It  will  be  unnecessary  to  include  a  protocol  here,  for  the 
method  has  been  utilized  to  determine  the  efficiency  of  the  irrigation 
process  after  the  introduction  into  the  lungs  of  different  substances, 
including  coloring  matters,  non-pathogenic  and  pathogenic  bacteria. 
The  protocols  that  follow  indicate  the  efficiency  of  the  method. 

Pn-6i.  June  16,  1918.  An  insufflation  of  20  c.c.  of  a  dilute  solution  of 
starch  paste  was  followed  by  a  continuous  perfusion  for  twenty-five 
minutes  of  3000  c.c.  of  salt  solution.  Throughout  the  exjjeriment  the  effluent 
continued  to  give  a  positive  iodine-starch  reaction.  At  the  end  of  the  per- 
fusion the  dog  was  killed.  The  lungs  were  removed  and  after  the  different 
lobes  had  been  cut  with  several  incisions  at  different  levels,  they  were 
tested  for  the  iodine  reaction.  A  positive  reaction  was  secured  with  the 
lower  right  lobe.  The  starch  was  uneven  in  its  distribution.  All  of  the 
larger  bronchi  and  the  majority  of  the  smaller  ones  were  free  of  starch. 

Pn-62.  June  16,  19 1 8.  The  above  experiment  with  Pn-6i  was  con- 
trolled by  injecting  Pn-62  with  the  same  amount  of  starch  paste  and  test- 
ing the  lungs  in  the  same  manner  without  the  perfusion.  The  lower  right 


1264     INTRATRACHEAL  PULMONARY  IRRIGATION 

lobe  was  full  of  starch,  as  was  also  a  portion  of  the  adjacent  upper  lobe. 
All  of  the  bronchi  from  the  large  ones  to  those  microscopic  in  size  were 
filled  with  the  paste. 

Pn-99.  Insufflation  of  15  c.c.  of  a  very  heavy  twenty-four-hour  broth 
culture  of  B.  prodigiosus.  The  tracheal  cannula  was  removed  and  sterilized. 
Saline  perfusion  of  the  lung  to  the  amount  of  3000  c.c,  lasting  forty-five 
minutes,  was  started  about  twenty  minutes  after  the  introduction  of  the 
culture.  The  perfusion  was  by  the  intermittent  method.  At  intervals 
during  the  perfusion  samples  were  taken  from  the  effluent.  These  were 
plated  in  dilutions  for  the  bacterial  count  of  B.  prodigiosus. 


Samples  after  Perfusion  of                     Count  per  Cubic  Centimeter 

300  c.c.                                                 .                2,075,000 

600  c.c.                                                                    970,000 

1000  c.c.                                                                    260,000 

2000  c.c.                                                                      90,000 

3000  c.c.                                                                      80,000 

These  two  experiments  demonstrate  conclusively  that  inert 
foreign  material  can  be  washed  out  by  the  method  of  intratracheal 
pulmonary  irrigation,  but  even  after  prolonged  treatment  of  this 
kind,  in  which  n\any  liters  of  irrigating  fluid  are  employed,  there 
still  remains  a  residue  of  the  original  material  introduced. 

The  experiment  with  B.  prodigiosus,  in  which  96  per  cent  of  the 
organisms  were  recovered  in  the  effluent,  was  most  encouraging, 
and  led  to  the  further  experiment  in  which  a  virulent  organism  was 
employed  as  a  measure  of  the  efficiency  of  the  treatment.  The  cul- 
ture selected  was  a  pneumococcus  Type  I,  which,  when  grown  in 
broth  for  eighteen  hours,  possessed  such  virulence  that  0.00000 1  c.c. 
was  uniformly  fatal  for  mice  within  forty-eight  hours.  Throughout 
the  experiment  this  culture  was  maintained  by  animal  passage  at 
this  virulence,  and  all  insufflations  were  made  with  eighteen-hour 
broth  cultures.  Preliminary  experiments  showed  that  20  c.c.  were 
required  to  produce  a  fatal  pneumonia  when  insufflated  by  the  intra- 
tracheal route  into  the  lung  of  a  dog,  and  although  the  animal 
became  ill,  death  never  followed  when  even  as  much  as  15  c.c.  of 
this  culture  was  utilized.  These  preliminary  experiments  were  fol- 
lowed by  another  group,  in  which  first  lethal  and  then  sublethal 
quantities  of  culture  were  insufflated  and  followed  by  irrigation. 
Despite  the  fact  that  over  75  per  cent  of  the  organisms  introduced 


INTRATRACHEAL  PULMONARY  IRRIGATION      1265 

were  recovered  in  the  effluent  by  actual  count,  the  animals  invariably 
succumbed  with  a  diffuse  pneumonia  involving  many  lobes. 

A  typical  protocol  in  which  a  sublethal  quantity  of  culture  was 
utilized  is  appended. 

Pn-VI.  January  27,  19 19.  Ten  cubic  centimeters  of  a  culture  of  pneu- 
mococcus  Type  I  were  introduced  by  intratracheal  insufflation  at  9.50 
A.M.  This  was  immediately  followed  by  an  intermittent  intrapulmonary 
irrigation  with  6000  c.c.  of  salt  solution.  The  dog  recovered  from  the  treat- 
ment, but  grew  more  and  more  prostrate  and  appeared  very  sick  at  9.30 
P.M.  He  survived  the  night,  but  died  at  10.35  a.m.,  January  28,  1919. 

Blood  for  culture  was  taken  after  the  irrigation  as  follows: 


Blood  Taken  at 

Interval  Since  Insuffla- 
tion 

Plate  Count  per  cc 

2.15  P.M. 

4       hours 

no  growth 

4.30  P.M. 

6yi  hours 

6 

7.00  P.M. 

10       hours 

332 

9.30  P.M. 

12       hours 

850 

10.40  A.M.    January  28,  1919 

(post-mortem) 

infinity 

The  effluent  was  collected  at  different  stages  during  the  irrigation  and 
each  specimen  was  plated.  The  individual  counts  for  each  sample  multi- 
plied by  the  volumes  give  the  following  figures  as  indicating  the  number  of 
organisms  washed  out: 

Sample  A,  233,450  per  c.c.  Total  number,  198,432,500 

Sample  B,  242,200  per  c.c.  Total  number,  448,070,000 

Sample  C,  94,000  per  c.c.  Total  number,  136,300,000 

Sample  D,  104,000  per  c.c.  Total  number,     33,280,000 

816,082,500 

This  figure  (816,082,500),  when  compared  with  the  number  of  or- 
ganisms introduced  (1,072,000,000),  shows  that  during  the  irrigation  76 
per  cent  of  the  organisms  were  eliminated  from  the  lung. 

Needless  to  say,  the  result  of  the  experiments  with  virulent 
organisms  in  such  sharp  contrast  to  those  with  saprophytic  bacteria 
was  unexpected  and  has  led  to  considerable  speculation.  It  will  be 
seen  that  one-half,  and  in  other  tests  a  much  smaller  number  of 
organisms  than  represent  a  minimal  lethal  dose,  a  quantity  which 
would  cause  the  animal  no  inconvenience  if  their  introduction  into 
the  lung  was  not  followed  by  the  irrigation  procedure,  results  in  a 
very  diffuse  and  fulminating  lobar  consolidation. 


1266     INTRATRACHEAL  PULMONARY  IRRIGATION 

Several  possibilities  suggest  themselves:  that  the  irrigation  dam- 
ages the  lung  to  a  sufficient  extent  to  allow  the  few  bacteria  that 
remain  to  develop  rapidly;  that  the  bacteria  multiply  even  during 
the  short  time  that  the  irrigation  is  proceeding,  and,  finally,  that  the 
flow  of  fluid  through  the  lung  drives  some  of  the  organisms  so  deep 
into  the  alveoli  that  they  become  more  firmly  lodged  and  rapidly 
multiply.  Probably  all  these  factors  play  a  r6Ie.  The  rapid  develop- 
ment of  the  septicemia  is  in  favor  of  pulmonary  damage  as  well  as 
mechanical  washing  of  the  organisms  into  the  deeper  tissues  of  the 
lung.  It  is,  however,  not  our  purpose  to  discuss  this  phase  of  the 
question. 

The  experiment  quoted  above  is  absolute  evidence  that  irrigation 
of  the  lung  with  salt  solution  not  only  cannot  be  utilized  to  advan- 
tage, but  is  actually  a  disseminator  and  an  aggravator  of  the  inflam- 
matory process  within  the  lung. 

The  above  experiments  indicate  conclusively  that  a  mechanical 
removal  by  the  irrigation  process  is  inadequate,  and  immediately 
suggests  the  use  of  very  dilute  chemical  disinfectants  or  specific  or 
non-specific  biological  agents. 

A  number  of  experiments  have  been  conducted  in  which  chemical 
disinfectants  were  used  as  irrigating  substances,  but  these  so  far 
have  resulted  in  the  production  of  pneumonias  which  are  analogous 
to  those  that  have  since  been  reported  by  WoIIstein  and  Meltzer  (5) 
and  which  are  designated  by  them  as  chemical  pneumonia.  It  is 
hoped  that  a  disinfecting  agent  may  be  used  sufficiently  dilute  to 
be  effective  and  yet  not  harmful,  and  that  other  specific  or  non- 
specific biological  agents  may  be  found  that  will  render  this  new 
route  of  pulmonary  therapy  effective. 

BIBLIOGRAPHY 

1.  WoIIstein  and  Meltzer,  J.  Exper.  M.,  1918,  XXVIII,  551. 

2.  "Collected  Studies  on  the  Pathology  of  War  Gas  Poisoning,"  Yale 

Univ.  Press  (in  press). 

3.  Winternitz  and  Lambert,  J.  Exper  M.,  1919. 

4.  Winternitz,  Mil.  Surgeon,  May,  19 19. 

5.  WoIIstein  and  Meltzer,  J.  Exper.  M.,  1918,  XXVIII,  547. 


ENVOI 

SIR   WILLIAM   OSLER   AND   THE   AMERICAN   MEDICAL   OFFICER 

By  Brig.-General  Francis  A.  Winter,  M.  C,  U.  S.  Army, 

Commandant,  Army  Medical  School,  Washington,  D.  C 

\^  LL  England  abounded  in  hospitality  for  the  American  cousin 
/■A  during  the  summer  of  191 8.  My  duties  placed  me  there,  and 
^  jLI  saw  that  the  spirit  of  welcome  made  no  specifications  of 
rank.  To  the  medical  officer,  the  great  centers  of  medical  thought 
and  teaching  in  London,  Leeds,  and  other  cities  held  forth  the 
unending  invitation,  but  there  remained  one  host  embodying  within 
himself  a  whole  medical  center,  and  Sir  William  Osier  furnished  the 
attraction  and  the  recompense. 

The  door  of  the  lovely  home  at  Oxford  had  no  latchstring — it 
was  simply  perennially  open  to  the  American  medical  officer  sta- 
tioned in  England,  or  transiently  stopping  there. 

There  was  motive  a  plenty  in  going  to  Oxford  to  see  the  leader, 
but  a  newer  and  a  stronger  impulse  to  go  again  came  to  him  who 
went  once,  in  the  welcome  which  he  found  and  the  inspiration  and 
uplift  he  carried  away.  It  was  the  easier  to  love  one's  kind,  and 
make  the  necessary  sacrifice  for  them,  when  one  had  sat  in  the  warm 
glow  of  the  fine  spirit,  which  enveloped  the  listener,  with  the  amiable 
and  instructive  counsel  and  good  fellowship  of  his  kindly  heart 
and  keen  mind. 

It  was  a  rare  privilege  to  be  able  to  go  to  Oxford  as  Oxford,  but 
to  go  there  and  be  met  by  the  living  sage,  to  induct  one  into  the 
atmosphere  of  the  sages  gone  before,  was  to  do  a  thing  marking  a 
red-letter  day. 

But  the  gentle  sage  did  not  rest  satisfied  that  he  should  do  no 
seeking,  and  straightway  he  came  to  all  our  hospitals,  whether  to 
speak  to  a  local  clinical  meeting,  to  raise  an  American  flag,  or  look 
over  the  state  of  our  sick,  and  I  doubt  that  he  will  ever  in  any 
degree  realize  the  response  his  inspiriting  presence  evoked  in  the 

1267 


1268  ENVOI 

hearts  of  the  elders  and  the  youngsters  who  sat  in  his  presence. 
Who  of  those  men  were  not  his  disciples,  for  who  had  not  read  the 
fascinating  pages  of  his  cornerstone  of  modern  medical  practice? 
Our  good  Sir  William — for  we  Americans  cannot  forego  our 
partnership  in  him — lent  all  that  was  at  his  command  to  the  ad- 
vancement of  American  interests  in  England,  and  how  he  helped 
us  is  a  grateful  and  a  delightful  recollection  to  those  of  us  whose 
military  fortunes  were  cast  in  the  mother  country  during  the  period 
of  the  war.  The  whole  world  of  medicine  lays  its  tribute  at  his  feet, 
and  from  no  element  in  that  broad  concourse  is  the  tribute  more 
instinct  with  love  and  admiration  than  in  the  little  offering  made 
by  us  of  the  A.  E.  F.  in  England. 


[the  end] 


Date  Due 


CAT    NO.   24    161 
pniNTED  IN  U.S.A-  \.f^i-    '^'-' 


